Abnormal uterine bleeding induced by glucocorticoid treatment for pemphigus

Patient 1

A 40-year-old woman with a 3-month history of red, peeling, and painful gingival erosions was referred to our clinic. On the basis of results of intraoral examinations, laboratory tests, and histopathological and direct immunofluorescence assays, a definitive diagnosis of oral PV was made (Figure 1A, C-E). According to the Japanese guidelines for pemphigus management, an initial dose of 0.5 mg/kg of glucocorticoids is recommended for pemphigus merely involving the oral mucosa, and the dose could be upregulated from 0.5 to 1 mg/kg depending on the lesion extent and disease severity.8 Therefore, the patient (body weight: 50 kg) was treated with oral glucocorticoids (prednisone acetate tablets, 25 mg, once daily), combined with immunosuppressants (thalidomide, 75 mg, once daily) and topical glucocorticoid application (dexamethasone paste, 0.05 mg/mL, 3 times daily). After 3 weeks, all the original lesions began to heal without the appearance of any new lesions. However, the patient complained of prolonged (>10 days compared with her average) and heavy menstrual flow during the treatment. These symptoms disappeared immediately after she discontinued prednisone. The patient took only medications that we had prescribed and had previously experienced regular menstrual cycles and volume. This was her first experience of abnormally excessive uterine bleeding. A gynecologist and physician were consulted to exclude organic diseases that may cause uterine bleeding. No related gynecological diseases, bleeding disorders, or systemic diseases were detected. Hence, a diagnosis of AUB was made. As the oral PV could not be well controlled without the use of oral glucocorticoid treatment, the administration of oral prednisone was reattempted (prednisone acetate tablets, 40 mg, once daily) during the non-menstrual period. However, AUB recurred and persisted until oral prednisone treatment was withdrawn. To control the oral PV, the treatment was changed to the intralesional injection of glucocorticoids (betamethasone) in combination with immunosuppressants and topical glucocorticoid application. After 2 weeks, all the lesions began to heal. Most importantly, the AUB did not recur. The treatment was again changed to a combination of oral thalidomide, biweekly intralesional betamethasone injection, and topical application of dexamethasone paste. After 4 months, all the lesions had healed without any evidence of AUB (Figure 1B).

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Figure 1

Clinical manifestation, hematoxylin and eosin (H&E) staining assay, and direct immunofluorescence (DIF) assay in a patient with pemphigus vulgaris (PV): A) Gingival lesion (black arrows) of the PV patient before treatment, B) The gingival lesion healed (black arrows) after treatment, C) H&E staining (40×) showed acantholysis in the spinous layer and intraepithelial blister formation (black arrow), D) DIF showed fishnet-like deposition of immunoglobin G between epithelial spinous cells (white arrow), and E) DIF also displayed fishnet-like deposition of complement C3 between epithelial spinous cells (white arrow).

In addition to the above-mentioned case, we also treated 2 other PV patients who experienced AUB during the non-menstrual period following glucocorticoid administration (Table 1). Both patients had normal menstruation and were definitively diagnosed with AUB following glucocorticoid administration via gynecological and physical examinations after the exclusion of organic diseases.

Patient 2

Her case involved relatively diffuse bullous erosions in the gingiva at the bilateral posterior mandibular area and bilateral abdomen of the tongue, and the initial dose of prednisone acetate used was 40 mg, once daily. The symptoms were well controlled at 2 weeks after treatment. Nevertheless, AUB developed 10 days after oral prednisone application, and spontaneously disappeared after one week, without any change in the treatment.

Patient 3

She exhibited localized lesions in the oral cavity, which was initially treated with a combination of thalidomide (75 mg, once daily) and intralesional injection of betamethasone (0.7 mg per week). The lesions were well-controlled following treatment. Nevertheless, AUB developed 5 days after the intralesional glucocorticoid injection. Although the administration mode was immediately changed to topical glucocorticoid application (dexamethasone paste), the AUB persisted without any sign of remission. Therefore, glucocorticoid treatment was withdrawn and the AUB resolved. Thereafter, treatment was switched to non-glucocorticoid medications (thalidomide, 75 mg, once daily). In these 2 patients, disease remission, without any recurrence of AUB, was noted at follow-up.