Dapsone for Recalcitrant Eosinophilic Annular Erythema: A Case Report and Literature Review

Patients with EAE classically present with recurrent erythematous or urticarial arcuate and annular plaques on the trunk and proximal extremities [1]. Clinically, EAE is described as presenting in one of two patterns: first as a figurate/centrifugum-type pattern reminiscent of deep erythema annulare centrifugum, or second as an urticarial/annular-type pattern [2]. It is devoid of bulla, though there is a single case report of bullous eosinophilic annular erythema with negative direct immunofluorescence and negative indirect IF as well [3].

Histologically, EAE is described as having a dense superficial and deep perivascular and/or interstitial lymphohistiocytic infiltrate with abundant eosinophils. It typically presents without “flame figures,” though they have been noted in some cases and with more longstanding lesions (polymorphism, multicenter). There are some reports of focal interface changes, but generally it is absent of mucin deposition, flame figures, vasculitis, or granulomas. Basal melanosis and pigment incontinence are also reported and may account for clinically observed dusky-toned areas of hyperpigmentation [4]. While still debatable, EAE is generally regarded as being distinct from annular erythema of infancy (AEI) and Wells syndrome (WS) (Table 1). Though it also shows tissue eosinophilia, erythema of infancy predominantly affects children under the age of 1 year and resolves spontaneously [2]. Wells syndrome presents as tender cellulitis-type plaques, though annular and figurate lesions can occur [2]. Many physicians, however, feel that EAE is a subset or variant of WS. In WS, the inflammatory cells, including eosinophils, often involve the dermis and subcutis, whereas in EAE they are generally confined to the dermis [4]. WS also features flame figures that are quite characteristic as well as blood eosinophilia, both of which are not typical of EAE. In addition to WS, the differential diagnosis may also include the deep form of erythema annulare centrifugum, tumid lupus erythematosus, Jessner lymphocytic infiltrate, urticarial bullous pemphigoid, erythema migrans, granuloma annulare, and interstitial granulomatous dermatitis [5].

The etiology of EAE remains largely unknown, though it is suggested that it may be a hypersensitivity reaction to an unidentified antigen [6]. It has been associated with several chronic conditions, such as autoimmune thyroid disease (both hypothyroidism and hyperthyroidism), chronic borreliosis, chronic H. pylori gastritis, chronic kidney disease, diabetes mellitus, and hepatitis C virus infection [5, 7]. Though suspected to be a hypersensitivity response, it has also been associated with internal malignancy. Specific malignancies have been reported in three cases, including thymoma with complete resolution following thymectomy [7], metastatic prostate adenocarcinoma [8], and renal carcinoma [9].

EAE is most commonly reported to respond successfully to systemic steroids and antimalarials, but it typically runs a chronic relapsing and remitting course, with a relapse frequently seen after discontinuing both treatments. It often shows resistance to multiple treatments. Most reports in the literature note the use of antimalarials as the first line for EAE. Response to hydroxychloroquine is typically prompt and usually observed within the first 4 weeks, though a case showing a delayed response with remission at 10 weeks has been reported [10]. Though Wells syndrome has been successfully treated with dapsone, there has been only one report prior to this one of a successful response of EAE to dapsone. That case report noted a complete response to dapsone at 25 mg qd, with the response occurring within 3 weeks and remission sustained at 8 months of follow-up [11]. Another multicenter study of 10 patients with EAE noted a chronic course and resistance to treatment with systemic steroids alone or in combination with hydroxychloroquine and cyclosporine [9]. Researchers reported that EAE is characterized by a chronic course, resistance to treatment, and a high relapse rate [9]. A single case report noted a response to eight sessions of narrow-band UVB following the failure of systemic steroids and hydroxychloroquine; the light therapy cleared the EAE without inducing pigment changes, and no recurrence was noted 9 months after the light therapy had been stopped [1]. There is also a single case report of a dramatic improvement with indomethacin, but repeated syncopal episodes apparently led to the cessation of that therapy [12]. A recent case showed remission with nicotinamide at 900 mg/day dosing [13]. Though the patient had previously required systemic steroids for 7 years, remission was maintained with nicotinamide for a full year after cessation of the steroids. The patient also had a history of autoimmune pancreatitis with elevated immunoglobulin G4 levels (335 mg/dl), but the case report did not comment on the treatment of that or its timing in relation to the EAE.

As one can see from these reports in the literature, EAE commonly runs a chronic relapsing course and is resistant to numerous treatments. Though EAE typically is refractory, it can also be self-limited; treatment may not be required in all instances [6].