Are You Confident of the Diagnosis?
Eosinophilic annular erythema (EAE) is a rare, benign skin condition that was first described in the literature by Kahofer et al in 2000 as a recurrent annular erythema with marked tissue eosinophilia and the absence of “flame figures.” The condition was initially reported in children by Peterson and Jarratt in 1981 as Annular Erythema of Infancy (AEI).
Characteristic findings on physical examination
Eosinophilic annular erythema presents clinically as a cutaneous eruption of solitary or multiple erythematous nodules or papules that migrate and evolve to form figurate, annular plaques with a clear center and an elevated erythematous border. The lesions generally manifest on the trunk and extremities with rare involvement of the face, axilla or groin reported in the literature. The plaques may vary in size from 1-30 cm, correlating to their duration. The lesions may persist for weeks to years before resolving without scarring with intermittent episodes of remission and recurrence.
The lesions of EAE may present asymptomatically, although pruritic or tender lesions have been reported. While systemic symptoms are generally absent, some patients have experienced constitutional symptoms in the form of fever, malaise, body ache, lethargy and arthralgia.
Expected results of diagnostic studies
A skin biopsy is necessary to make and confirm the diagnosis of EAE. Histologically, EAE is characterized by a dense superficial and deep dermal perivascular and interstitial lymphohistiocytic infiltrate with abundant eosinophils. Basal vacuolar degeneration and dermal mucin deposition have been described in a few cases. Classically, “flame figures” have been absent in the majority of cases of EAE, which may help distinguish the condition from Wells syndrome, in which they are a frequent, often diagnostic, finding; their presence has been reported in lesions of long-standing duration in some patients. Eosinophilic degranulation and granulomatous formations also may be observed and are reported infrequently in the literature. Direct immunofluorescence is usually negative.
Complete blood count may be normal or blood eosinophilia may be observed. Further serologic testing should be considered based on the history and presentation to include comprehensive metabolic profile, erythrocyte sedimentation rate and C-reactive protein, Rheumatoid factor, ANA, liver and thyroid function tests, serologic testing for Borrelia burgdorferi and rickettsial species, and stool examination for ova and parasites.
Eosinophilic Annular Erythema must be distinguished primarily from Wells Syndrome and Annular Erythema of Infancy. Wells Syndrome presents as burning or itching skin that develops into edematous plaques and is characterized histologically by a diffuse eosinophilic infiltrate of the dermis and by “flame figures,” collagen fibers coated with deposits of eosinophilic major basic protein. EAE does not present with burning and generally lacks flame figures. Annular Erythema of Infancy is differentiated from EAE by age of onset.
The differential diagnosis of EAE includes other cutaneous figurate erythemas, insect bites and drug reactions. Erythema annulare centrifugum is differentiated from EAE as tissue eosinophilia is absent. Lupus erythematosus tumidus is associated with histologic changes not seen in EAE, such as lymphocytic inflammation, ample mucin deposits and positive direct immunofluorescence in 50% of cases; furthermore, tissue eosinophilia is also absent.
Jessner lymphocytic infiltration of the skin is also differentiated from EAE by the absence of tissue eosinophilia. Erythema chronicum migrans is distinguished from EAE by a superficial and deep perivascular lymphocytic infiltrate with peripheral plasma cells and central eosinophils. Erythema gyratum repens is a paraneoplastic rash that is similar to EAE histologically as a superficial perivascular lymphohistiocytic infiltrate that may include eosinophils. Granuloma annulare is distinguished by palisaded granuloma formation that is not observed in EAE.
Urticaria may be distinguished from EAE as prominent interstitial eosinophilia is absent. Urticarial bullous pemphigoid may consist of an eosiniophilic inflammatory infiltrate; however, unlike EAE there is a positive direct immunofluorescence for IgG and C3. Interstitial granulomatous dermatitis may be considered a differential diagnosis, as eosinophils may be present in a drug induced or autoimmune case. Sarcoidosis is distinguished from EAE by the presence of “naked” granulomas with scant lymphocytes.
Who is at Risk for Developing this Disease?
Eosinophilic annular erythema is a rare cutaneous disorder with no known risk factors.
What is the Cause of the Disease?
The etiology of eosinophilic annular erythema is not understood. It has been proposed to be a hypersensitivity reaction to an unknown antigen. The pathophysiology of EAE is not clear.
Systemic Implications and Complications
Associated systemic disorders that have been observed in patients with EAE include chronic gastritis with H. pylori, diabetes mellitus, chronic hepatic C virus infection, chronic kidney disease, autoimmune thyroid disease, chronic borreliosis and renal carcinoma.
See Table I.
Optimal Therapeutic Approach for this Disease
Treatment with topical and systemic corticosteroids may show improvement of skin lesions, although relapse is frequent. Systemic prednisone at a dose of 30-40 mg/day may effectively control the disease with therapeutic response observed in 3-4 weeks and significant improvement within 8-11 weeks.
Antimalarial therapy with chloroquine or hydroxychloroquine often shows marked improvement and complete resolution of the disease with a dose of 200-400 mg/day for 2 weeks and can be considered a first-line agent alone or in combination with a synthetic corticosteroid. If antimalarial agents are contraindicated, cyclosporine at 2.5 mg/kg/day may be used in combination with synthetic corticosteroids and has been shown to have a therapeutic response in 3-5 weeks with significant control after 10-11 weeks.
A dramatic response has been observed in treatment with oral indomethacin at a dose of 25 mg three times a day with an almost complete resolution of skin lesions within 5 days; however, this medication may not be well tolerated and syncopal episodes should warrant discontinuation.
A significant improvement with any treatment modality may not be achieved in patients who have had the disease for more than 4 years, though regression in size of lesions may be observed with relapse after treatment cessation. Proper management of associated systemic diseases can improve rates of relapse and lengthen the remission period.
The patient should be told that eosinophilic annular erythema is a benign disease that is often self-limited and may resolve spontaneously over the course of months to years with intermittent periods of relapse. The patient’s goals for treatment should be discussed and aesthetic and symptomatic concerns should be addressed when determining appropriate therapeutic intervention.
Unusual Clinical Scenarios to Consider in Patient Management
Eosinophilic annular erythema does not appear to be a severe disease; although it has rarely been associated chronic gastritis with H. pylori, diabetes mellitus, chronic hepatic C virus infection, chronic kidney disease, autoimmune thyroid disease, chronic borreliosis and renal carcinoma (one case). Follow-up may be warranted based on other presenting symptoms.
What is the Evidence?
El-Khalawany, M, Al-Mutairi, N, Sultan, M, Shaaban, D. “Eosinophilic annular erythema is a peculiar subtype in the spectrum of Wells syndrome: a multicenter long-term follow-up study”. J Eur Acad Dermatol Venereol. vol. 27. 2013. pp. 973-9. (A prospective multicenter study of histologic findings, laboratory results, therapeutic responses and follow-up of 10 patients with eosinophilic annular erythema followed by a conclusion that EAE is a variant of Wells syndrome.)
Howes, R, Girgis, L, Kossard, S. “Eosinophlic annular erythema: a subset of Well’s syndrome or a distinct entity?”. Australas J Dermatol. vol. 49. 2008. pp. 159-63. (A case report of eosinophilic annular erythema followed by a discussion of the histologic features that warrant distinction between eosinophilic annular erythema and Wells syndrome.)
Kahofer, P, Grabmaier, E, Aberer, E. “Treatment of eosinophilic annular erythema with chloroquine”. Acta Derm Venereol. vol. 80. 2000. pp. 70-1. (A case report of eosinophilic annular erythema treated successfully with chloroquine.)
Prajapati, V, Cheung-Lee, M, Schloss, E, Salopek, TG. “Spontaneously resolving eosinophilic annular erythema”. J Am Acad Dermatol. vol. 67. 2012. pp. e75-7. (A case report of eosinophilic annular erythema in a 54-year old woman that resolved spontaneously.)
Rongioletti, F, Fausti, V, Kempf, W, Rebora, A, Parodi, A. “Eosinophilic annular erythema: an expression of the clinical and pathological polymorphism of Wells syndrome”. J Am Acad Dermatol. vol. 65. 2011. pp. e135-7. (A report of four male patients with eosinophilic annular erythema with the histologic finding of “flame figures” in two of the patients followed by a discussion of EAE as a subset of Wells syndrome.)
Sempau, L, Larralde, M, Luna, PC, Casas, J, Staiger, H. “Eosinophilic annular erythema”. Dermatol Online J. vol. 18. 2012. pp. 8(A case report of eosinophilic annular erythema in a 15-year-old boy that resolved spontaneously followed by a discussion of the history, histopathology, and treatment of eosinophilic annular erythema.)
Heymann, WR. “Eosinophilic annular erythema: attention must be paid”. Skinmed. vol. 12. 2014. pp. 376-378. (A clinical review of EAE including perspectives on the controversies of nosology and etiology.)
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