Pemphigus foliaceus (PF) is a superficial vesiculobullous disease characterized by production of IgG4 antibodies targeting desmoglein 1, a protein important for epidermal cell–cell adhesion.1,2 Disruption of cell–cell adhesion causes acantholysis resulting in superficial, fragile blisters that are prone to rupture. Consequently, patients typically present with erosions rather than blisters.3 Typically, the lesions are well-demarcated and occur on the face or trunk. They tend to be disseminated, and localized presentations are rare. The incidence of PF varies between different populations, and the average age of onset is between 50 and 60 years.3 The pathogenesis of PF is not completely understood, but environmental exposure appears to be involved.2,4,5 We present an interesting case of a young woman with a difficult-to-treat, localized form of PF that was unrelated to any known triggers.

The patient was a 19-year-old Cuban-American woman who presented to our clinic with a 6-month history of eroded, erythematous, crusted lesions on the right side of her face. The lesions had been treated unsuccessfully with topical antifungals, antibiotics, and oral antibiotics for a presumed diagnosis of tinea or impetigo. The patient had no significant past medical history, and her only medications included oral contraceptives and occasional ibuprofen.

A physical examination revealed faint erythematous, eroded impetiginized patches on the right cheek and temple (Fig. 1). A culture from 1 lesion grew methicillin-sensitive staphylococcus aureus. Further laboratory studies were undertaken to screen for antinuclear antibodies, including anti-double-stranded DNA antibodies, and antibodies against the extractable nuclear antigens Smith, Ro, and La, and the histone proteins; the results were negative in all cases. A biopsy revealed superficial acantholysis and hyperchromatic nuclei in the granular layer, consistent with PF. Direct immunofluorescence studies demonstrated segmental intercellular staining with immunoglobulin (Ig) G and C3 (Fig. 2a and b). Enzyme-linked immunosorbent assay (ELISA) was negative for desmogleins 1 and 3. Based on these results, a diagnosis of PF was confirmed and the patient was started on clobetasol propionate 0.05% ointment with partial response. A trial of dapsone 100mg daily for 2 months resulted in no benefit. Prednisone 60mg daily with gradual taper induced clinical remission with no relapse during a follow-up of 18 months, except for a recent development of a single erythematous patch on the right cheek with confirmation of PF by direct immunofluorescence testing.

Figure 1.

Faint erythematous and eroded impetiginized patches on the right cheek and temple.

(0.16MB).

Figure 2.

(a) Superficial acantholysis and hyperchromatic nuclei in the granular layer (hematoxylin–eosin, original magnification ×20) and (b) DIF at 40× magnification displaying segmental intercellular staining for IgG and C3.

(0.25MB).

Localized PF is rare, and only 12 cases have been reported in the literature (Table 1)4,6–12; moreover, some of these cases later developed widespread lesions.6,7,12 Topical medications, such as imiquimod and nonsteroidal anti-inflammatory drugs, have been implicated in localized PF (Table 1).4,5 In contrast, to other cases reported, our patient was younger, she denied application of any topical medications, and the lesions did not become disseminated.

Despite the clinical impression of impetigo, the lack of response to appropriate antibiotic treatment and the persistence of the lesions prompted us to suspect an immunobullous disorder as the source of the secondarily impetiginized lesions. The presence of subcorneal acantholysis and intercellular staining demonstrated by direct immunofluorescence confirmed the diagnosis of PF: the histopathological features of bullous impetigo may be similar to those of PF, but immunopathology would be negative in bullous impetigo.2 In PF, ELISA testing of anti-desmoglein-1 antibodies is usually positive, with sensitivities as high as 97.9%,13 and this test has been found to have greater sensitivity and specificity than conventional indirect immunofluorescence (IIF).14 A positive ELISA was reported in two of the published cases of localized PF, and IIF results in these cases were variable (see Table 1). Interestingly, our patient had a negative ELISA but IIF results were positive.

With regard to management, topical steroids may be used for more localized lesions (see Table 1) but systemic steroids are currently the mainstay of treatment and were required in our patient to induce clinical remission.15 Other treatments, such as dapsone, failed in our case.

In conclusion, immunobullous disease should be suspected in presumed infectious disorders that are refractory to appropriate antimicrobial treatment. This case exemplifies the need for proper pathological and immunopathological studies to establish a diagnosis of this very unusual variant of PF.

The authors declare that they have no conflicts of interest.