Diagnostic difficulties in pediatric annular dermatoses

A one-and-a-half-year-old girl presented to our pediatric dermatology clinic with erythematous papules and annular succulent plaques with a greyish-green center, confined to the right buttock (Fig. 1a, b). The parents had been applying a topical steroid ointment prescribed by a private practitioner for a few days, without efficacy.

The child’s medical history included trigonocephaly for which she had had surgical reconstruction, but was otherwise uneventful.

Our initial clinical differential diagnoses included Wells’ syndrome and eosinophilic annular erythema of childhood.

Histopathology, obtained from the border of the red to the greyish area of an annular lesion, revealed a superficial and deep perivascular and interstitial lymphocytic infiltrate with abundant CD68-positive macrophages (Fig. 1c, d).

White blood cell count and eosinophils were within the normal range. Eosinophilic cationic protein (ECP) and total serum IgE were both elevated, at 85.5 µg/L (normal value 13.3 µg/L) and 22.0 klU/L (age-adapted reference value < 10 kU/L), respectively. Family history of atopy and specific IgE antibodies to common inhalant and nutritive allergens were negative.

The lesions were treated with topical clobetasol propionate and occlusive dressing for 10 days, followed by once daily application that led to complete remission within 3 consecutive weeks. Since then, the patient has remained asymptomatic for the past 9 months without any further therapy.

Annular dermatoses in pediatric patients include a broad spectrum of differential diagnoses that can only be definitely diagnosed based on subtle clinical variations in conjunction with histopathologic features. In some cases, laboratory investigations are mandatory to rule out serious complications (Table 1).

Annular erythema of infancy (AEI) and eosinophilic annular erythema (EAE) of childhood are described as distinct, rare inflammatory conditions of infancy and childhood [1‐5]. There are only a few cases previously published in the literature; therefore, the true incidence of these dermatoses is unknown and is likely underreported [1‐7].

In 1981, Peterson and Jarratt originally coined the term AEI, for recurrent rapidly evolving arcuate and annular benign skin lesions, predominantly in infants from 3 to 11 months of age with spontaneous resolution within the first year of life. Histology consists of perivascular lymphocytes with scattered eosinophils [6]. Histiocytic infiltration has been described in HE staining but neither in that abundancy nor immunohistochemically (Fig. 1c, d; [7]). In contrast, EAE is thought to represent the morphological expression of a spectrum of eosinophilic dermatoses in older children that often follow a more recalcitrant clinical course, requiring immunomodulatory drugs. Histology shows a superficial and deep, predominantly perivascular, lymphocytic infiltrate with abundant eosinophils without “flame figures,” which are characteristic, but not pathognomonic, for Wells’ syndrome [1, 3, 8]. The only differences between AEI and EAE are the age of disease onset and the eosinophil count in histology (some in AEI and abundant in EAE), which results in a more transient rash in AEI or recalcitrant in EAE [3, 8].

Wells’ syndrome is a rare pruritic inflammatory skin disease of unknown etiology with several morphologic variants that have been described in recent years (papulonodular, papulovesicular, plaque-type, urticarial, or bullous). It classically presents as localized erythematous swelling (hence the term eosinophilic cellulitis), and subsequently progresses to indurated plaques with a characteristic green-greyish hue in the central part of the plaque.

In the present case, clinical findings were primarily compatible with Wells’ syndrome. The lack of eosinophils in histology, however, suggests otherwise, leaving room for debate. The natural tissue lifespan of eosinophils ranges from 2 to 5 days.⁷ Treatment with topical steroids downregulates interleukin (IL)-5, which is crucial for the recruitment and survival of eosinophils in tissue [9]. In hindsight it can only be speculated whether prior topical steroid treatment could obscure histopathologic findings (i.e., eradicate all tissue eosinophils).

Elevated levels of ECP in the absence of peripheral eosinophilia as well as the clinical presentation of annular succulent plaques with a greyish-green center (Fig. 1a, b) indicate eosinophil activation.

The age of onset after the first year of life would suggest EAE as the favorable diagnosis, while Wells’ syndrome does not have an age-specific predilection and is even considered to be rare in children [3, 8]. From our own experience, we know that Wells’ syndrome is probably underdiagnosed in many patients due to its polymorphic picture, as we have seen and successfully treated three children alone in the past 2 years. As the etiology is elusive in many cases, we propose that eosinophilic annular dermatoses in children might pose an academically unsatisfactory diagnostic dilemma. It remains to speculate whether they are different presentations of an identical pathophysiological process that lie within a spectrum and should not be exclusive of one another.