Successful methotrexate treatment of oesophageal pemphigus vulgaris in an immunosuppressed patient with Crohn's disease.

A 32-year-old Caucasian man was admitted to our department for evaluation of oesophageal erosions that had persisted for one year (Fig. 1A and 1B). On admission a small erosion was observed on his soft palate. The patient had a history of recalcitrant Crohn’s disease, with colon manifestation at 17 years of age. An early colectomy was performed as the patient’s condition was unresponsive to systemic immunosuppression. However, the small bowel subsequently became involved, requiring various immunosuppressive therapies including systemic prednisolone, azathioprine, mercaptopurine, adalimumab, and certolizumab. On admission, the patient’s Crohn’s disease was stable on treatment with 400 mg certolizumab monotherapy s.c. bi-weekly. The patient was also on prednisolone 60 mg/day orally (0.82 mg/kg body weight) due to oesophageal lesions. Oesophageal Crohn’s disease, PV, and persistent erosive infection were taken into consideration. The prednisolone dose was tapered below 10 mg, resulting in a severe relapse. Yeast, human herpes virus 1–5, HIV, hepatitis B+C, and syphilis infections were excluded. Indirect immunofluorescence revealed linear intercellular epithelial staining on monkey oesophagus (titre 1:40). Both desmoglein 1 and 3 enzyme-linked immunoassays (ELISAs) were positive (titres 44.1 and 47.4 AU/ml, respectively; cut-off: 20 AU/ml). However, direct immunofluorescence on repeated, multiple (7 oesophageal and 2 oral) perilesional biopsies were negative, although acantholysis could be observed. To prove that the circulating autoantibodies are indeed pathogenic, an in vitro keratinocyte dissociation assay was performed confirming pathogenicity (Fig. 1C). In addition to 60 mg oral prednisolone daily, the patient received 2 g/kg body weight intravenous immunoglobulins monthly and azathioprine up to 3 mg/kg body weight daily, but the dose of prednisolone could not be tapered below 20 mg daily, and azathioprine was hepatotoxic. Thus, azathioprine was replaced by methotrexate in increasing doses up to 30 mg weekly. The prednisolone dose could be reduced to 10 mg daily, but further reduction led to relapse, requiring a long-term maintenance dose of 10 mg daily. At the 2-year follow-up, the patient was free of signs or symptoms of PV on a combination of prednisolone (10 mg daily), methotrexate (30 mg weekly) and immunoglobulins.