Pemphigus of the eyelids

ARTICLE

Pemphigus is an autoimmune blistering disease divided into two major subtypes: pemphigus vulgaris (PV) and pemphigus foliaceus (PF) [1-3]. The autoimmune target of pemphigus is desmoglein (Dsg), a cadherin type of cell to cell adhesion molecule found in desmosomes [2]. Patients with PF have only anti-Dsg 1 IgG autoantibody [4-9], whereas PV patients are further subdivided into a mucosal dominant type (PV-M) and a mucocutaneous type (PV-MC) [4, 10]. PV-M clinically shows predominant oral erosions with limited skin involvement, which shows no more than 5 or 6 scattered or isolated erosions or blisters, no larger than 5 cm in diameter [4, 10]. On the other hand, PV-MC shows extensive skin involvement in addition to oral involvement. PV-M has only anti-Dsg 3 IgG, but not anti-Dsg 1, while PV-MC has both anti-Dsg 3 and anti-Dsg 1 IgG [4, 10]. The case of PV reported here showed an unusual clinical appearance on the lower eyelids involving both anti-Dsg 3 and anti-Dsg 1 antibodies.

Case report

A 56-year-old Japanese woman exhibiting small papules on the lower eyelids with itching (Fig. 1A) and widespread oral erosion with pain (Fig. 1B) consulted Department of Dermatology, Ogaki Municipal Hospital on March 7, 2000. Two months before consultation, oral erosion had appeared on her oral hard palate and buccal membrane. Several small papules with less than 1 mm in diameter with erythema had been noticed on her lower eyelids and two brown papules less than 1 mm in diameter on the left upper eyelid for 3 days. No involvement was found in other skin areas or conjunctiva. She had no history of drug allergies or other skin diseases. Her medical history showed no systemic diseases or the use of specific long-term medication. Laboratory data were within normal range. A smear test of the erosion on oral mucosa using Giemsa stain showed some Tzanck cells without any multinucleated giant cells. Histopathological examination of a skin specimen from a small papule with 0.8 mm in diameter on the right lower eyelid (shown by an arrow in Figure 1A) revealed suprabasal cleft and acantholysis in the lower epidermis (Fig. 2). The basal cells remained attached to the dermis like "a row of tombstones". An inflammatory infiltration with lymphocytes, neutrophils and eosinophils was found in the upper dermis. Histopathological findings for the oral membrane also showed acantholysis in the lower mucous membrane. Intercellular deposits of IgG (Fig. 3A) and C3 were seen in the whole epidermis of the papule on the right lower eyelid by direct immunofluorescence study. These deposits were also observed in the biopsy specimen from erosion on the left buccal membrane. IgA, IgM and C1q were negative by direct immunofluorescence study. Indirect immunofluorescence study using normal human skin as a substrate showed intercellular antibodies directed to the cell surface of the whole epidermis with a titer of 1:40 (Fig. 3B). The titers of antibodies to Dsgs 3 and 1 were 118 and 25.9, respectively, by enzyme-linked immunosorbent assay (ELISA). Based on these clinical and histopathological features and the immunofluorescence study, a diagnosis of pemphigus vulgaris was made.

The patient was treated with an oral administration of prednisolone (0.75 mg/kg/day) for 9 days and topical betamethasone valerate ointment (0.06% ointment, once a day) for skin eruptions on the eyelids for 3 days from March 27. These treatments improved the oral erosion and skin eruptions. The eruptions on the eyelids had disappeared before April 10 and slight dark brown pigmentation was left on the lower eyelids where the skin eruptions had existed. However, the small erosion on the hard palate continued until April 26 and disappeared before May 2. The dose of oral prednisolone was gradually tapered and reached 0.13 mg/kg/day as a maintenance dose on May 17. Prednisolone administration was ceased from June 7.

Discussion

A clinical diagnosis of PV was made in the present case from the clinical and histopathological features and immunofluorescence study. However, tiny papules on the bilateral eyelids with itching were an unusual clinical appearance of PV. Syringoma, herpes simplex and verruca planae were clinically considered as differential diagnosis and the small size of the papules in this case could have made it difficult to identify them as vesicles. A diagnosis of PV was made from histological findings of the papule showing suprabasal cleft and acantholysis in the lower epidermis, and intercellular deposits of IgG and C3 in the whole epidermis by direct immunofluorescence study. We speculated that the vesicles might have been formed by rubbing eyelids because of itching as a Nikolsky sign.

A diagnosis of PV-M was made in this case, because the oral erosions were predominant with limited skin involvement. A cut off value has been suggested as 11.0 for Dsg 1 ELISA, an index value above 20.0 is considered to be positive, and the value between these has been defined to be a gray zone [6, 10]. Therefore, both antibodies to Dsgs 3 and 1 were positive, although the titer of antibody to Dsg 1 was not so high. PV-M usually has only antibody to Dsg 3 but not to Dsg 1 [4, 10]. In general, PV-MC tends to be generalized and, therefore, more severe than PV-M [10]. It has been reported that the mean duration of PV-M is 3.25 months and that of PV-MC is 6.28 months concerning disease duration [10]. In the present case, prednisolone (0.75 mg/kg/day) was effective on skin eruptions on the eyelids. However, it took more than 1 month until oral erosion disappeared and 6 more weeks to cease the treatment with prednisolone. In conclusion, it is suggested that this patient may be a rare case of PV-M diagnosed from the view of clinical and histopathological findings. However, the possibility of PV-MC cannot be denied in spite of limited skin involvement, because antibodies to Dsgs 1 and 3 are positive.

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