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Mycophenolate mofetil in autoimmune and inflammatory skin disorders
Journal of the American Academy of Dermatology Volume 40, Number 2, Part 1
Brief communications 265
Mycophenolate mofetil in autoimmune and inflammatory skin disorders Hossein C. Nousari, MD, Alexander Sragovich, MD, Arash Kimyai-Asadi, MD, Diane Orlinsky, MD, and Grant J. Anhalt, MD Baltimore, Maryland Mycophenolate mofetil (MMF) has been widely used as an immunosuppressant in organ transplantation. MMF has recently been added to therapeutic regimens for skin disorders. Expanding the use of MMF in dermatology, we describe additional patients with autoimmune and inflammatory skin diseases, including 4 cases of pemphigus vulgaris, 1 case of pemphigus foliaceus, 1 case of perineal and metastatic cutaneous Crohn’s disease, 1 case of bullous pemphigoid and psoriasis, and 1 case of psoriasis. Most of these patients had refractory disease or had developed significant side effects to conventional therapy, including azathioprine, methotrexate, prednisone, cyclosporine, acitretin, PUVA, UVB, and tacrolimus. MMF was effective and well tolerated in all these patients. The dosages of MMF ranged from 500 mg twice daily (for psoriasis and Crohn’s disease) to 1250 mg twice daily (for 3 of 4 patients with pemphigus vulgaris). MMF is an effective and relatively safe immunosuppressant in autoimmune and inflammatory skin diseases. (J Am Acad Dermatol 1999;40:265-8.)
Mycophenolate mofetil (MMF) is a recent addition to the therapeutic armamentarium of dermatologic diseases such as pemphigus vulgaris,1 bullous pemphigoid (BP),2,3 pyoderma gangrenosum,4,5 psoriasis,6 and dyshidrotic eczema.7 Expanding the use of MMF in dermatology, we describe additional patients with autoimmune and inflammatory skin disorders that were successfully treated in our institution with MMF. CASE REPORTS We present 1 case of metastatic cutaneous Crohn’s disease, 1 case of pemphigus foliaceus, 4 cases of pemphigus vulgaris, 1 case of BP and psoriasis, and 1 case of psoriasis, all of which were successfully treated with MMF. We will discuss 4 representative cases in some detail; Table I summarizes all 8.
Case 1: Perineal and metastatic cutaneous Crohn’s disease A 33-year-old African-American woman with a 15year history of intestinal Crohn’s disease was only partially responsive to sulfasalazine and high-dose oral and intravenous corticosteroids. She could not tolerate From the Department of Dermatology, Johns Hopkins Medical Institutions. Reprints are not available from the authors. Copyright © 1999 by the American Academy of Dermatology, Inc. 0190-9622/99/$8.00 + 0 16/54/94730
cyclosporine or tacrolimus because of seizures, or azathioprine because of severe pancytopenia. Despite quiescent intestinal disease, she had perineal and metastatic Crohn’s disease manifested by painful perivulvar ulcers and bilateral inguinal and inframammary linear ulcerated plaques histologically consistent with cutaneous Crohn’s disease. Five months of prednisone 60 mg/day and methotrexate 15 mg/week failed to control the cutaneous disease. Prednisone was slowly tapered and she was given oral thalidomide 100 mg/day for 2 months. Because of only partial improvement, MMF 500 mg twice a day was added. A dramatic response was observed at 6-month follow-up. She has tolerated the regimen without complications, the perineal skin lesions are completely healed, and the inguinal and inframammary lesions are painless and almost healed. She is currently receiving MMF 500 mg twice a day and thalidomide 100 mg/day.
Case 2: BP and psoriasis A 62-year-old man with a long-standing history of plaque-type psoriasis partially controlled with topical steroids and tar experienced BP. He required doses of prednisone up to 140 mg/day to control the BP. Tapering prednisone to below 40 mg/day was associated with flares of both psoriasis and BP. He also suffered from hypertension, non-insulin-dependent diabetes mellitus, osteoporosis with several lumbar vertebral fractures, and prominent cushingoid features. He was given MMF 1 g twice a day and prednisone
Journal of the American Academy of Dermatology February 1999
266 Brief communications
Table I. Clinical features, response to therapy, and tolerance to MMF in 8 patients Case
Age (y)/ Sex
Diagnosis
MMF (dose)
Adjunctive therapy
1
33/F
Cutaneous perineal and metastatic Crohn’s
500 mg bid
Thalidomide 100 mg/day
CSA, AZP, MTX prednisone, FK 506
Good (see text)
2
62/M
BP, psoriasis
1 g bid
Prednisone rapid taper
Prednisone up to 140 mg/day
Good (see text)
3
55/M
PF
1 g bid
Prednisone taper
AZP 250 mg/day
Good (see text)
4
66/F
PV (oral)
1250 mg bid
Prednisone taper
AZP 200 mg/day
Good (see text)
5
54/F
PV (mucocutaneous)
1250 mg bid
Prednisone taper
AZP 200 mg/day
6
25/F
PV (mucocutaneous)
1250 mg bid
Prednisone taper
AZP 200 mg/day
7
53/M
PV (oral)
1000 mg bid
Prednisone taper
Prednisone 80 mg/day
8
48/F
Psoriasis (generalized plaque type)
500 mg bid
Topical steroids, calcipotriol
PUVA, UVB, MTX, acitretin
Complete clearing of oral & skin lesions at 6 month F/U; no side effects Complete AZP-induced clearing of nausea; steroidoral & skin induced mucosal lesions at 8 candidiasis month F/U; no side effects Complete No response; clearing of steroid-induced oral lesions diabetes at 5 month F/U; no side effects Almost No response to complete phototherapy and clearing of acitretin; MTXlesions at 6 induced month F/U; hepatotoxicity no side effects.
Previous therapy
Response & tolerance
Reasons for MMF
No response or severe side effects from previous immunosuppressive therapy Flare of psoriasis upon tapering prednisone and steroidinduced lumbar vertebral fractures AZP-induced hepatotoxicity and no response to prednisone alone AZP-induced nausea, steroidinduced diabetes with recurrent mucosal candidiasis AZP-induced hepatotoxicity; steroid-induced depression
AZP, Azathioprine; BP, bullous pemphigoid; CSA, cyclosporine; FK 506, tacrolimus; F/U, follow-up; MF, mycophenolate mofetil; PF, pemphigus foliaceus; PV, pemphigus vulgaris.
was tapered to 5 mg/day. Complete clearing of BP and dramatic improvement of psoriasis lesions were achieved within 4 months. He has tolerated MMF without side effects.
Case 3: Pemphigus foliaceus A 55-year-old man with a history of pemphigus foliaceus who responded only partially to a 2-month course of prednisone 1 mg/kg daily experienced hepatotoxici-
Journal of the American Academy of Dermatology Volume 40, Number 2, Part 1
ty manifested by highly elevated serum liver enzymes when treated with azathioprine 3 mg/kg daily. A switch to MMF 1 g twice a day resulted in progressive improvement within 5 weeks of therapy, allowing a gradual taper of prednisone. Six months later, while receiving prednisone 10 mg/day and MMF 1 g twice a day, his lesions have cleared completely and he has tolerated the regimen without side effects.
Case 4: Pemphigus vulgaris A 66-year-old woman with extensive oral pemphigus vulgaris responsive to prednisone 1 mg/kg daily would relapse each time the prednisone dose was reduced to below 35 mg/day. She experienced noninsulin-dependent diabetes mellitus and recurrent mucosal candidiasis requiring oral fluconazole. Azathioprine 3 mg/kg daily was not tolerated because of intractable nausea, so MMF 1 g twice a day was started. Within 4 weeks of therapy, her prednisone could be tapered to 20 mg/day. To achieve complete clearing of the lesions, MMF was increased to 1250 mg twice a day. At 6-month follow-up only a few healing superficial erosions in the buccal mucosa remained. She is currently taking prednisone 10 mg every other day and MMF 1250 mg twice a day. This therapeutic regimen has been well tolerated. DISCUSSION
In February 1997, the Food and Drug Administration approved MMF for the prevention of renal allograft rejection. The effectiveness and safety of MMF as an immunosuppressant have extended its use to other immune-mediated conditions.8-13 MMF is the morpholinyl ethyl ester prodrug of mycophenolic acid (MPA), initially isolated from Penicillium spp. MMF was synthesized to increase MPA bioavailability. MMF is well absorbed orally but is rapidly conjugated to its glucuronide form in the liver and kidney and eliminated in the urine. This inactive glucuronide form cannot penetrate cell membranes, but certain tissues such as the human epidermis express the enzyme β-glucuronidase, which converts inactive MPA glucuronide back into its active form.8,9 MPA interferes with de novo purine synthesis by inhibiting type II inosine monophosphate dehydrogenase, an enzyme expressed in stimulated T and B lymphocytes.8 MMF is usually well tolerated. The principal adverse reactions associated with MMF include diarrhea, nausea, vomiting, abdominal cramping, reversible mild anemia, leukopenia, and infection.8,9 These side effects are generally seen in
Brief communications 267 patients receiving more than 2 g/day or who simultaneously receive other immunosuppressants. There is a debatable increase in the incidence of lymphoproliferative malignancies with the use of MMF.14-17 Our patients with autoimmune and inflammatory skin diseases were treated successfully with MMF. The exact dosage and monitoring of MMF is still an ongoing area of research. Measurement of inosine monophosphate dehydrogenase activity in lymphocytes or serum levels of MPA or MPA glucuronide may be promising in terms of the degree of immunosuppression brought about by MMF.18,19 The usual dosage in organ transplantation is 2 g/day, but in this scenario MMF is always combined with high doses of prednisone, cyclosporine, or tacrolimus. Our preliminary data may indicate that patients with autoimmune blistering disorders, particularly pemphigus vulgaris, require higher doses of MMF than those used in inflammatory dermatoses. Of 4 cases of pemphigus vulgaris, 3 required MMF 2.5 g/day to control the disease. However, large studies should be performed to establish appropriate therapeutic dosages in dermatologic patients. The adjuvant therapies in these 8 cases included prednisone tapers, thalidomide, topical steroids, and calcipotriol. Because these agents alone and often at higher doses were unable to control the disease, the improvement seen after MMF addition is likely caused by MMF. From our experience, MMF has been an effective and relatively safe immunosuppressant and immunomodulatory drug in autoimmune and inflammatory skin diseases. Larger studies should be undertaken in the future to further clarify the efficacy and safety of MMF in the treatment of autoimmune and inflammatory skin diseases. REFERENCES 1. Enk AH, Knop J. Treatment of pemphigus vulgaris with mycophenolate mofetil [letter]. Lancet 1997;350:494. 2. Bohm M, Beisert S, Shwarz T, et al. Bullous pemphigoid treated with mycophenolate mofetil [letter]. Lancet 1997;349:541. 3. Nousari HC, Griffin WA, Anhalt GJ. Successful therapy of bullous pemphigoid with mycophenolate mofetil. J Am Acad Dermatol 1998;39:497-8. 4. Hohenleutner U, Mohr VD, Michel S, Landthaler M. Mycophenolate mofetil and cyclosporine treatment for recalcitrant pyoderma gangrenosum [letter]. Lancet 1997;350:1748. 5. Nousari HC, Lynch W, Petri M, Anhalt GJ. The effectiveness of mycophenolate mofetil in refractory pyoderma gangrenosum. Arch Dermatol In press.
Journal of the American Academy of Dermatology February 1999
268 Brief communications 6. Haufs MG, Beissert S, Grabbe S, Schutte B, Luger TA. Psoriasis vulgaris treated successfully with mycophenolate mofetil. Br J Dermatol 1998;138:179-81. 7. Picknacker A, Luger TA, Schwarz T. Dyshidrotic eczema treated with mycophenolate mofetil. Arch Dermatol 1998;134:378-9. 8. Lipsky JJ. Mycophenolate mofetil. Lancet 1996;348: 1357-9. 9. Silverman Kitchin JE, Keltz Pomeranz M, Pak G, et al. Rediscovering mycophenolic acid: review article of its mechanism, side effects, and potential use. J Am Acad Dermatol 1997;37:445-9. 10. Nowack R, Birck R, van der Woude FJ. Mycophenolate mofetil for systemic vasculitis and IgA nephropathy [letter]. Lancet 1997;349:774. 11. Gavlik A, Goldberg MG, Tsaroucha A, et al. Mycophenolate mofetil rescue therapy in liver transplant recipients. Transplantation Proc 1997;29:549-52. 12. Taylor DO. The use of tacrolimus and mycophenolate mofetil after cardiac transplantation. Curr Opin Cardiol 1997;12:161-5. 13. Zimmer-Molsberger B, Knauf W, Thiel E. Mycophenolate mofetil for severe autoimmune haemolytic anemia. Lancet 1997;350:1003-4. 14. Epinette WW, Parker CM, Jones EL, Greist MC. Mycophenolic acid for psoriasis: a review of pharmacol-
15.
16.
17.
18.
19.
ogy, long-term efficacy, and safety. J Am Acad Dermatol 1987;17:962-71. European Mycophenolate Mofetil Cooperative Study Group. Placebo-controlled study of mycophenolate mofetil combined with cyclosporine and corticosteroids for prevention of acute rejection. Lancet 1995;345: 1321-5. Solinger HW, US Renal Transplant Mycophenolate Mofetil Study Group. Mycophenolate mofetil for the prevention of acute rejection in cadaveric renal allograft recipients. Transplantation 1995;60:225-32. The Tricontinental Mycophenolate Mofetil Renal Transplantation Study Group. A blinded, randomized clinical trial of mycophenolate mofetil for the prevention of acute rejection in cadaveric renal transplantation. Transplantation 1996;61:1029-37. Greismacher A, Weigel G, Seebacher G, Muller MM. IMP-dehydrogenase inhibition in human lymphocytes and lymphoblasts by mycophenolic acid and mycophenolic acid glucuronide. Clin Chem 1997;43:2312-7. Kaplan B, Gruber SA, Nallamathou R, Katz SM, Shaw LM. Decreased protein binding of mycophenolic acid associated with leukopenia in a pancreas transplant recipient with renal failure. Transplantation 1998;65: 1127-9.
Brief communications 265
Mycophenolate mofetil in autoimmune and inflammatory skin disorders Hossein C. Nousari, MD, Alexander Sragovich, MD, Arash Kimyai-Asadi, MD, Diane Orlinsky, MD, and Grant J. Anhalt, MD Baltimore, Maryland Mycophenolate mofetil (MMF) has been widely used as an immunosuppressant in organ transplantation. MMF has recently been added to therapeutic regimens for skin disorders. Expanding the use of MMF in dermatology, we describe additional patients with autoimmune and inflammatory skin diseases, including 4 cases of pemphigus vulgaris, 1 case of pemphigus foliaceus, 1 case of perineal and metastatic cutaneous Crohn’s disease, 1 case of bullous pemphigoid and psoriasis, and 1 case of psoriasis. Most of these patients had refractory disease or had developed significant side effects to conventional therapy, including azathioprine, methotrexate, prednisone, cyclosporine, acitretin, PUVA, UVB, and tacrolimus. MMF was effective and well tolerated in all these patients. The dosages of MMF ranged from 500 mg twice daily (for psoriasis and Crohn’s disease) to 1250 mg twice daily (for 3 of 4 patients with pemphigus vulgaris). MMF is an effective and relatively safe immunosuppressant in autoimmune and inflammatory skin diseases. (J Am Acad Dermatol 1999;40:265-8.)
Mycophenolate mofetil (MMF) is a recent addition to the therapeutic armamentarium of dermatologic diseases such as pemphigus vulgaris,1 bullous pemphigoid (BP),2,3 pyoderma gangrenosum,4,5 psoriasis,6 and dyshidrotic eczema.7 Expanding the use of MMF in dermatology, we describe additional patients with autoimmune and inflammatory skin disorders that were successfully treated in our institution with MMF. CASE REPORTS We present 1 case of metastatic cutaneous Crohn’s disease, 1 case of pemphigus foliaceus, 4 cases of pemphigus vulgaris, 1 case of BP and psoriasis, and 1 case of psoriasis, all of which were successfully treated with MMF. We will discuss 4 representative cases in some detail; Table I summarizes all 8.
Case 1: Perineal and metastatic cutaneous Crohn’s disease A 33-year-old African-American woman with a 15year history of intestinal Crohn’s disease was only partially responsive to sulfasalazine and high-dose oral and intravenous corticosteroids. She could not tolerate From the Department of Dermatology, Johns Hopkins Medical Institutions. Reprints are not available from the authors. Copyright © 1999 by the American Academy of Dermatology, Inc. 0190-9622/99/$8.00 + 0 16/54/94730
cyclosporine or tacrolimus because of seizures, or azathioprine because of severe pancytopenia. Despite quiescent intestinal disease, she had perineal and metastatic Crohn’s disease manifested by painful perivulvar ulcers and bilateral inguinal and inframammary linear ulcerated plaques histologically consistent with cutaneous Crohn’s disease. Five months of prednisone 60 mg/day and methotrexate 15 mg/week failed to control the cutaneous disease. Prednisone was slowly tapered and she was given oral thalidomide 100 mg/day for 2 months. Because of only partial improvement, MMF 500 mg twice a day was added. A dramatic response was observed at 6-month follow-up. She has tolerated the regimen without complications, the perineal skin lesions are completely healed, and the inguinal and inframammary lesions are painless and almost healed. She is currently receiving MMF 500 mg twice a day and thalidomide 100 mg/day.
Case 2: BP and psoriasis A 62-year-old man with a long-standing history of plaque-type psoriasis partially controlled with topical steroids and tar experienced BP. He required doses of prednisone up to 140 mg/day to control the BP. Tapering prednisone to below 40 mg/day was associated with flares of both psoriasis and BP. He also suffered from hypertension, non-insulin-dependent diabetes mellitus, osteoporosis with several lumbar vertebral fractures, and prominent cushingoid features. He was given MMF 1 g twice a day and prednisone
Journal of the American Academy of Dermatology February 1999
266 Brief communications
Table I. Clinical features, response to therapy, and tolerance to MMF in 8 patients Case
Age (y)/ Sex
Diagnosis
MMF (dose)
Adjunctive therapy
1
33/F
Cutaneous perineal and metastatic Crohn’s
500 mg bid
Thalidomide 100 mg/day
CSA, AZP, MTX prednisone, FK 506
Good (see text)
2
62/M
BP, psoriasis
1 g bid
Prednisone rapid taper
Prednisone up to 140 mg/day
Good (see text)
3
55/M
PF
1 g bid
Prednisone taper
AZP 250 mg/day
Good (see text)
4
66/F
PV (oral)
1250 mg bid
Prednisone taper
AZP 200 mg/day
Good (see text)
5
54/F
PV (mucocutaneous)
1250 mg bid
Prednisone taper
AZP 200 mg/day
6
25/F
PV (mucocutaneous)
1250 mg bid
Prednisone taper
AZP 200 mg/day
7
53/M
PV (oral)
1000 mg bid
Prednisone taper
Prednisone 80 mg/day
8
48/F
Psoriasis (generalized plaque type)
500 mg bid
Topical steroids, calcipotriol
PUVA, UVB, MTX, acitretin
Complete clearing of oral & skin lesions at 6 month F/U; no side effects Complete AZP-induced clearing of nausea; steroidoral & skin induced mucosal lesions at 8 candidiasis month F/U; no side effects Complete No response; clearing of steroid-induced oral lesions diabetes at 5 month F/U; no side effects Almost No response to complete phototherapy and clearing of acitretin; MTXlesions at 6 induced month F/U; hepatotoxicity no side effects.
Previous therapy
Response & tolerance
Reasons for MMF
No response or severe side effects from previous immunosuppressive therapy Flare of psoriasis upon tapering prednisone and steroidinduced lumbar vertebral fractures AZP-induced hepatotoxicity and no response to prednisone alone AZP-induced nausea, steroidinduced diabetes with recurrent mucosal candidiasis AZP-induced hepatotoxicity; steroid-induced depression
AZP, Azathioprine; BP, bullous pemphigoid; CSA, cyclosporine; FK 506, tacrolimus; F/U, follow-up; MF, mycophenolate mofetil; PF, pemphigus foliaceus; PV, pemphigus vulgaris.
was tapered to 5 mg/day. Complete clearing of BP and dramatic improvement of psoriasis lesions were achieved within 4 months. He has tolerated MMF without side effects.
Case 3: Pemphigus foliaceus A 55-year-old man with a history of pemphigus foliaceus who responded only partially to a 2-month course of prednisone 1 mg/kg daily experienced hepatotoxici-
Journal of the American Academy of Dermatology Volume 40, Number 2, Part 1
ty manifested by highly elevated serum liver enzymes when treated with azathioprine 3 mg/kg daily. A switch to MMF 1 g twice a day resulted in progressive improvement within 5 weeks of therapy, allowing a gradual taper of prednisone. Six months later, while receiving prednisone 10 mg/day and MMF 1 g twice a day, his lesions have cleared completely and he has tolerated the regimen without side effects.
Case 4: Pemphigus vulgaris A 66-year-old woman with extensive oral pemphigus vulgaris responsive to prednisone 1 mg/kg daily would relapse each time the prednisone dose was reduced to below 35 mg/day. She experienced noninsulin-dependent diabetes mellitus and recurrent mucosal candidiasis requiring oral fluconazole. Azathioprine 3 mg/kg daily was not tolerated because of intractable nausea, so MMF 1 g twice a day was started. Within 4 weeks of therapy, her prednisone could be tapered to 20 mg/day. To achieve complete clearing of the lesions, MMF was increased to 1250 mg twice a day. At 6-month follow-up only a few healing superficial erosions in the buccal mucosa remained. She is currently taking prednisone 10 mg every other day and MMF 1250 mg twice a day. This therapeutic regimen has been well tolerated. DISCUSSION
In February 1997, the Food and Drug Administration approved MMF for the prevention of renal allograft rejection. The effectiveness and safety of MMF as an immunosuppressant have extended its use to other immune-mediated conditions.8-13 MMF is the morpholinyl ethyl ester prodrug of mycophenolic acid (MPA), initially isolated from Penicillium spp. MMF was synthesized to increase MPA bioavailability. MMF is well absorbed orally but is rapidly conjugated to its glucuronide form in the liver and kidney and eliminated in the urine. This inactive glucuronide form cannot penetrate cell membranes, but certain tissues such as the human epidermis express the enzyme β-glucuronidase, which converts inactive MPA glucuronide back into its active form.8,9 MPA interferes with de novo purine synthesis by inhibiting type II inosine monophosphate dehydrogenase, an enzyme expressed in stimulated T and B lymphocytes.8 MMF is usually well tolerated. The principal adverse reactions associated with MMF include diarrhea, nausea, vomiting, abdominal cramping, reversible mild anemia, leukopenia, and infection.8,9 These side effects are generally seen in
Brief communications 267 patients receiving more than 2 g/day or who simultaneously receive other immunosuppressants. There is a debatable increase in the incidence of lymphoproliferative malignancies with the use of MMF.14-17 Our patients with autoimmune and inflammatory skin diseases were treated successfully with MMF. The exact dosage and monitoring of MMF is still an ongoing area of research. Measurement of inosine monophosphate dehydrogenase activity in lymphocytes or serum levels of MPA or MPA glucuronide may be promising in terms of the degree of immunosuppression brought about by MMF.18,19 The usual dosage in organ transplantation is 2 g/day, but in this scenario MMF is always combined with high doses of prednisone, cyclosporine, or tacrolimus. Our preliminary data may indicate that patients with autoimmune blistering disorders, particularly pemphigus vulgaris, require higher doses of MMF than those used in inflammatory dermatoses. Of 4 cases of pemphigus vulgaris, 3 required MMF 2.5 g/day to control the disease. However, large studies should be performed to establish appropriate therapeutic dosages in dermatologic patients. The adjuvant therapies in these 8 cases included prednisone tapers, thalidomide, topical steroids, and calcipotriol. Because these agents alone and often at higher doses were unable to control the disease, the improvement seen after MMF addition is likely caused by MMF. From our experience, MMF has been an effective and relatively safe immunosuppressant and immunomodulatory drug in autoimmune and inflammatory skin diseases. Larger studies should be undertaken in the future to further clarify the efficacy and safety of MMF in the treatment of autoimmune and inflammatory skin diseases. REFERENCES 1. Enk AH, Knop J. Treatment of pemphigus vulgaris with mycophenolate mofetil [letter]. Lancet 1997;350:494. 2. Bohm M, Beisert S, Shwarz T, et al. Bullous pemphigoid treated with mycophenolate mofetil [letter]. Lancet 1997;349:541. 3. Nousari HC, Griffin WA, Anhalt GJ. Successful therapy of bullous pemphigoid with mycophenolate mofetil. J Am Acad Dermatol 1998;39:497-8. 4. Hohenleutner U, Mohr VD, Michel S, Landthaler M. Mycophenolate mofetil and cyclosporine treatment for recalcitrant pyoderma gangrenosum [letter]. Lancet 1997;350:1748. 5. Nousari HC, Lynch W, Petri M, Anhalt GJ. The effectiveness of mycophenolate mofetil in refractory pyoderma gangrenosum. Arch Dermatol In press.
Journal of the American Academy of Dermatology February 1999
268 Brief communications 6. Haufs MG, Beissert S, Grabbe S, Schutte B, Luger TA. Psoriasis vulgaris treated successfully with mycophenolate mofetil. Br J Dermatol 1998;138:179-81. 7. Picknacker A, Luger TA, Schwarz T. Dyshidrotic eczema treated with mycophenolate mofetil. Arch Dermatol 1998;134:378-9. 8. Lipsky JJ. Mycophenolate mofetil. Lancet 1996;348: 1357-9. 9. Silverman Kitchin JE, Keltz Pomeranz M, Pak G, et al. Rediscovering mycophenolic acid: review article of its mechanism, side effects, and potential use. J Am Acad Dermatol 1997;37:445-9. 10. Nowack R, Birck R, van der Woude FJ. Mycophenolate mofetil for systemic vasculitis and IgA nephropathy [letter]. Lancet 1997;349:774. 11. Gavlik A, Goldberg MG, Tsaroucha A, et al. Mycophenolate mofetil rescue therapy in liver transplant recipients. Transplantation Proc 1997;29:549-52. 12. Taylor DO. The use of tacrolimus and mycophenolate mofetil after cardiac transplantation. Curr Opin Cardiol 1997;12:161-5. 13. Zimmer-Molsberger B, Knauf W, Thiel E. Mycophenolate mofetil for severe autoimmune haemolytic anemia. Lancet 1997;350:1003-4. 14. Epinette WW, Parker CM, Jones EL, Greist MC. Mycophenolic acid for psoriasis: a review of pharmacol-
15.
16.
17.
18.
19.
ogy, long-term efficacy, and safety. J Am Acad Dermatol 1987;17:962-71. European Mycophenolate Mofetil Cooperative Study Group. Placebo-controlled study of mycophenolate mofetil combined with cyclosporine and corticosteroids for prevention of acute rejection. Lancet 1995;345: 1321-5. Solinger HW, US Renal Transplant Mycophenolate Mofetil Study Group. Mycophenolate mofetil for the prevention of acute rejection in cadaveric renal allograft recipients. Transplantation 1995;60:225-32. The Tricontinental Mycophenolate Mofetil Renal Transplantation Study Group. A blinded, randomized clinical trial of mycophenolate mofetil for the prevention of acute rejection in cadaveric renal transplantation. Transplantation 1996;61:1029-37. Greismacher A, Weigel G, Seebacher G, Muller MM. IMP-dehydrogenase inhibition in human lymphocytes and lymphoblasts by mycophenolic acid and mycophenolic acid glucuronide. Clin Chem 1997;43:2312-7. Kaplan B, Gruber SA, Nallamathou R, Katz SM, Shaw LM. Decreased protein binding of mycophenolic acid associated with leukopenia in a pancreas transplant recipient with renal failure. Transplantation 1998;65: 1127-9.