Pediatric Dermatology, Pruritic Annular Vesiculobullous Plaques in a 10‐Year‐Old Female

A 10-year-old healthy female presented with a 1.5-year history of a persistent, waxing and waning pruritic rash. It began on the lower legs and spread to her arms, chest and face. Her history was negative for any preceding or concurrent fever or other systemic symptoms. She had no medication or infectious exposures. The rash had mild improvement with mometasone furoate 0.1% cream once daily for 2 weeks and significant improvement with 5 days of oral prednisolone. On examination, thin annular pink papules and plaques with superficial erosions and hemorrhagic crusting were present on the lower extremities with milder involvement of the arms (Figures 1 and 2). Several small discrete vesicles were present on her lower legs bilaterally and there were a few crusted papules on her face. A wound swab for bacterial culture and herpes simplex virus (HSV) polymerase chain reaction (PCR) were collected from the crusted papules on her face. She was empirically started on cephalexin for presumed bacterial superinfection. Shave biopsies were obtained from an intact 1 mm vesicle on the left medial ankle for H&E stain (Figure 3) and from perilesional skin for direct immunofluorescence (DIF) (Figure 4). The bacterial culture grew Streptococcus mitis and Staphylococcus aureus, both sensitive to cephalexin. HSV 1 and 2 PCRs were negative. The biopsy showed an intraepidermal vesicle with eosinophilic spongiosis and spongiform pustules. There was a perivascular infiltrate of lymphocytes, eosinophils, and neutrophils (Figure 3, H&E 11× magnification). The histopathological differential diagnosis included superficial forms of pemphigus, partially re-epithelialized bullous pemphigoid, and linear IgA bullous dermatosis (LABD). DIF demonstrated deposition of IgG and C3 within the epithelial intercellular spaces, without IgA, IgM, or fibrinogen. No linear deposition of immunoreactants was found along the basement membrane zone. This DIF pattern was consistent with pemphigus (Figure 4, DIF 20× magnification). A pemphigus IgG serum antibody panel demonstrated positive desmoglein (Dsg) 1 IgG (602 U/mL) and negative Dsg3 IgG (1 U/mL), consistent with a Dsg1 subtype of pemphigus. Taken with her clinical findings, a diagnosis of pemphigus herpetiformis (PH) was made. PH is a rare subtype of pemphigus with even rarer occurrence in the pediatric population [1, 2]. Skin lesions are pruritic and morphologically can be vesiculobullous or papular in grouped and annular patterns. Annular configurations mimic other autoimmune bullous diseases such as LABD, IgA pemphigus and dermatitis herpetiformis (DH). PH usually spares the mucous membranes [3]. Diagnostic criteria for PH have been suggested, including typical clinical features with DIF findings of intercellular IgG and/or C3 in the epithelium [3, 4]. Others have proposed additional findings, including intraepidermal eosinophils, neutrophils or both and/or an intraepidermal split with or without acantholysis, and detection of serum autoantibodies against Dsg (1, 3), or desmocollins (1–3) or both [5]. In the most comprehensive literature review of 158 PH cases including children, 75% of those who had ELISA studies available (81/158) showed reactivity to Dsg1 [5]. Positive anti-Dsg1 autoantibody is not specific for PH but does support the diagnosis [4]. Differentiating PH from pemphigus vulgaris (PV) and pemphigus foliaceus (PF) is important as the treatments and disease prognoses differ. PV and PH both have intercellular DIF staining with IgG. However, the autoantibodies in PV target Dsg3 or Dsg3/1. Clinically, PV has mucosal involvement, which is lacking in PH, and flaccid bullae with painful erosions on the skin, not pruritic blisters. While PF and PH both target Dsg1 and share DIF findings, they are clinically distinct. PF presents with erythematous crusted plaques with “cornflake” scale in a seborrheic distribution. In contrast, PH often involves the extremities with grouped to annular erythematous papules and vesicles. DH can clinically appear similar to PH; however, DH will show subepidermal separation with neutrophils in papillary tips with granular deposition of IgA in the dermal papillae on DIF. Serology is often positive for tissue transglutaminase. LABD shows subepidermal separation and linear IgA deposition along the basement membrane zone on DIF. Prior to the discovery of DIF, LABD was grouped with DH given similar findings of annular vesiculobullous plaques on extremities [6]. IgA pemphigus shows fragile intraepidermal vesicles and pustules on the trunk and extremities in an intertriginous distribution with IgA rather than IgG in the epidermal intercellular spaces on DIF. The prognosis of PH is excellent with treatment. No associations with comorbidities or malignancies in pediatric PH have been reported. Systemic steroids (0.5–2 mg/kg/day) with or without oral dapsone (0.5–2 mg/kg/day; maximum starting dose 50 mg/day) as the primary steroid-sparing agent is first-line therapy for PH [7]. Other steroid-sparing agents have been used as second-line therapies including azathioprine [8], mycophenolate mofetil [7], and methotrexate [9]. Relapses can occur, often during steroid taper. Duration of treatment ranges from 3 weeks to 24 months with partial to complete remission [2]. In contrast, while treatment of pediatric PV and PF also requires corticosteroids for rapid relief, immunosuppressive medications are typically necessary, including the use of rituximab to induce remission [6, 10]. Our patient's rash cleared on prednisone and has been maintained in remission on dapsone. The authors would like to thank the patient and family. In addition, the authors would also like to thank Kristin M. Leiferman, MD at the University of Utah (ARUP Laboratories) for their services. The authors declare no conflicts of interest.