To the Editor: A 57-year-old female presented with a 1-month history of pruritus and generalized annular erythema with blisters. The physical examination revealed widespread erythematous plaques with vesicles on her trunk and extremities (Fig 1). She also had proteinuria. Histopathologic examination of one of the blisters showed subepidermal splits and inflammatory infiltrates consisting of lymphocytes, neutrophils, and eosinophils. Direct immunofluorescence studies demonstrated linear deposits of immunoglobulin (Ig) G2 and C3 along the dermoepidermal junction. Indirect immunofluorescence microscopy of 1 M NaCl-split skin specimens revealed circulating IgG autoantibodies binding to the epidermal side. Using an enzyme-linked immunosorbent assay incorporating the NC16a domain recombinant protein (BP180NC16a), an index level for IgG antibody binding of 292.0 (cut-off value for a positive result is 9) was found in the patient's serum. Based on those findings, bullous pemphigoid (BP) was diagnosed, and treatment with 30 mg/day prednisolone commenced. The patient developed proteinuria from 0.75 g/day at baseline to 1.6 g/day. Because prednisolone treatment was not effective for the massive proteinuria, a renal biopsy was performed. Light microscopy showed thickening of the glomerular basement membrane without proliferation of mesangial cells or matrix expansion. Immunofluorescence microscopy revealed IgG1, IgG2, IgG3, and IgG4 deposition along the basement membranes of renal glomeruli, slightly positive for IgM and C3. Electron microscopy showed dense deposits below the epithelium of the basement membrane. Based on these findings, a diagnosis of membranous nephropathy was established. Even after 4 weeks of prednisolone (30 mg/day) therapy, the skin eruptions worsened and new blisters continued to appear. Examination of the urine revealed a gradual decrease in the degree of proteinuria. Prednisolone was increased (50 mg/day) and urinary abnormalities slightly improved. However, the skin eruptions continued to worsen. Therefore, combined therapy with mizoribine (150 mg daily) and prednisolone (50 mg daily) was initiated. Two weeks after initiation of that therapy, the blister formation ceased and the proteinuria improved. Currently, 6 months after tapering the prednisolone dosage, the patient has not had a recurrence of the eruptions or suffered significant adverse effects to the drugs. Urinalysis shows no recurrence of the proteinuria. One year later, the serum anti-BP180NC16a antibody level had declined to 31.4. Our patient responded favourably to mizoribine, which was added to supplement the prednisolone monotherapy, because that monotherapy had not produced a positive response. Mizoribine is a purine synthesis inhibitor that was recently developed as a new immunosuppressant in Japan; indications for its use have been extended to nephrotic syndromes, including membranous nephropathy.1Shibasaki T. Koyama A. Hishida A. Muso E. Osawa G. Yamabe H. et al.A randomized open-label comparative study of conventional therapy versus mizoribine onlay therapy in patients with steroid-resistant nephrotic syndrome (postmarketing survey).Clin Exp Nephrol. 2004; 8: 117-126Crossref PubMed Scopus (38) Google Scholar, 2Nishioka Y. Horita Y. Tadokoro M. Taura K. Suyama N. Miyazaki M. et al.Changing mizoribine administration from three divided doses to one single dose induced remission of relapsed membranous nephropathy.Nephrol Dial Transplant. 2006; 21: 2337-2338Crossref PubMed Scopus (5) Google Scholar Based on the reduction of anti-BP180NC16a antibodies from the combined treatment, we believe that this regimen has the potential to reduce antibody production.3Kobayashi M. Amagai M. Kuroda-Kinoshita K. Hashimoto T. Shirakata Y. Hashimoto K. et al.BP180 ELISA using bacterial recombinant NC16a protein as a diagnostic and monitoring tool for bullous pemphigoid.J Dermatol Sci. 2002; 30: 224-232Abstract Full Text Full Text PDF PubMed Scopus (178) Google Scholar, 4Tsuji-Abe Y. Akiyama M. Yamanaka Y. Kikuchi T. Sato-Matsumura K.C. Shimizu H. Correlation of clinical severity and ELISA indices for the NC16A domain of BP180 measured using BP180 ELISA kit in bullous pemphigoid.J Dermatol Sci. 2005; 37: 145-149Abstract Full Text Full Text PDF PubMed Scopus (95) Google Scholar It has recently been reported that 14-3-3 proteins, which are mizoribine-binding proteins, interact with the glucocorticoid receptor and may enhance the transcriptional activity of that receptor, suggesting a steroid-sparing effect of mizoribine.5Takahashi S. Wakui H. Gustafsson J.A. Zilliacus J. Itoh H. Functional interaction of the immunosuppressant mizoribine with the 14-3-3 protein.Biochem Biophys Res Commun. 2000; 274: 87-92Crossref PubMed Scopus (81) Google Scholar Mizoribine may be effective for treating patients refractory to corticosteroid monotherapy, while enabling a substantial reduction in the dose and side effects of corticosteroids. The addition of oral mizoribine to the regimen appears to have allowed tapering of the prednisolone and has prevented a disease relapse.