- Email: [email protected]
Treatment of severe lichen planus with mycophenolate mofetil
THERAPY
Treatment of severe lichen planus with mycophenolate mofetil Uta Frieling, MD, Gisela Bonsmann, MD, Thomas Schwarz, MD, Thomas A. Luger, MD, and Stefan Beissert, MD Mu ¨ nster, Germany Lichen planus (LP) is an inflammatory skin disorder with a wide range of clinical appearances. The treatment of disseminated and especially erosive forms of LP is often difficult and disappointing. Activated T cells are important in the pathogenesis of LP as indicated by the dermal lymphocytic infiltrate leading to keratinocyte destruction and lesion formation. Similar histologic findings are present in graft-versus-host disease. Since T cells are key players in the development of both disorders and mycophenolate mofetil has been successfully introduced in the treatment of graft-versus-host disease, we have examined the therapeutic potential of this agent in 3 patients suffering from disseminated and erosive LP. Mycophenolate mofetil was well tolerated and induced complete remission in 2 patients, and substantial improvement in the third patient. (J Am Acad Dermatol 2003;49:1063-6.)
L
ichen planus (LP) is a papulosquamous inflammatory disorder, which affects the skin, mucous membranes, nails, and hair follicles. LP usually occurs as a benign disease with spontaneous remissions and exacerbations. Nonetheless, therapeutic management of extensive disseminated and especially erosive LP can be challenging and discouraging for both the patient and the physician.1 Mucocutaneous lesions that are sometimes also ulcerated cause considerable discomfort and disability. In such patients, the treatment of choice is systemic immunosuppression. However, general immunosuppression may be limited by significant adverse effects. Therefore, the development of specialized immunosuppressive regimens that are better tolerated with minimal side effects is of particular practical relevance. A few years ago, a new immunosuppressive agent, mycophenolate mofetil (MMF), which specifically and reversibly inhibits the proliferation of activated T cells, was introduced in the treatment of autoimmune and inflammatory skin disorders.2-5 Furthermore, MMF has also been successfully used From the Department of Dermatology, University of Mu¨nster. Funding sources: None. Conflict of interest: None identified. Presented in part at the meeting of the German Dermatologic Society (DDG), Berlin, May 2001. Reprint requests: Stefan Beissert, MD, Department of Dermatology, Von-Esmarch-Str. 58, D-48149 Mu¨nster, Germany. E-mail: [email protected]. Copyright © 2003 by the American Academy of Dermatology, Inc. 0190-9622/2003/$30.00 ⫹ 0 doi:10.1016/S0190-9622(03)02111-X
in the treatment of graft-versus-host disease (GVHD).6 Both GVHD and LP are characterized by activated T cells, which play a pivotal role in lesion formation.7 Thus, we have used MMF for the treatment of LP in two patients who suffered from extensive, disseminated LP and in one patient with a severe, erosive, recalcitrant, mucocutaneous form of the disease. We report on the successful use of MMF in the management of these patients’ conditions.
CASE REPORTS Cases 1 and 2 A 34-year-old white woman and a 17-year-old white male patient presented with a 2- to 3-month history of extensive generalized LP including nonpainful Wickham’s striae of the buccal mucosa. Biopsies showed changes characteristic of LP. There was worsening of the disease on treatment with systemic (20 mg/d over 2 weeks) and potent topical corticosteroids (class II and III over 5 weeks) in the woman, and with potent topical corticosteroids (class III over 6-8 weeks) in the male patient. Both patients suffered from extreme pruritus. Review of systems together with laboratory analyses including hepatitis serologies was unremarkable. After exclusion of potential underlying disease contraindicated immunosuppressive therapy (eg, tuberculosis) and informed consent had been obtained, both patients received MMF 1 g twice daily. During the first weeks of treatment there was no marked improvement of the lesions, but pruritus diminished. Within 5 to 6 weeks of treatment all papulosquamous and oral reticulated lesions started to decrease. Complete remission was achieved after approximately 20 weeks 1063
1064 Frieling et al
J AM ACAD DERMATOL DECEMBER 2003
Table I. Summary of patients and treatments LP
MMF treatment
Mucosa
Case Sex/Age No. (y)*
Skin
Oral Genital
Duration (mo)
Previous treatment
Dosage/ (g/d)
Duration (mo)
Concurrent treatment
Therapeutic effects
Follow-up (mo)
1
F/34
dLP
rLP
/
2
SC, TC
2.0
5
/
CR
19
2
M/17
dLP
rLP
/
3
TC
2.0
5
/
CR
65
3
F/54
/
eLP
eLP
65
TC, SC 2.0 Hydroxy1.0 chloroquine 0.5 Dapsone 1.5 Acitretin 1.25 1.0 Azathioprine 0.75 Pulsed 1.0 cyclo0.75 phosphamide/ dexamethasone 0.75/0.5
12 6 2 8 2 2 1 9 2 2
MI Initially pulsed cyclophosphamide/ dexamethasone (9 mo)
46; MMF cont’d
CR, Complete remission; dLP, disseminated; eLP, erosive lichen planus; MI, marked improvement; rLP, reticulated lichen planus; SC, systemic corticosteroids; TC, topical corticosteroids. *Age at onset of disease.
of treatment. Medication was discontinued, and no new lesions developed during a follow-up period of 17 and 63 months, respectively, in the female and male patient. MMF was well tolerated without any side effects.
phic scarring persisted. Therapy was tolerated well without any side effects. In summary, quality of life in this patient was markedly improved with MMF therapy.
Case 3 A 59-year-old white female patient had a 5-year history of severe recalcitrant erosive LP of the oral and genital mucous membranes. Her past medical history was uneventful and she was taking no medication before the onset of the disease. Histology demonstrated typical features of erosive LP. Hepatitis serology was negative. Previous treatment included multiple other immunomodulating and immunosuppressive therapies. Since her disease was still uncontrolled, MMF was added at a dose of 1 g twice daily to the last treatment with pulsed cyclophosphamide/dexamethasone. After 9 months of this combination therapy, erosive lesions diminished and cyclophosphamide/dexamethasone pulses were discontinued. Subsequently, the lesions cleared and MMF was quickly reduced to 0.5 g twice daily. However, during the following months, she experienced two relapses when MMF was reduced below 1 g daily. Each time, her disease stabilized with an increased dose of MMF (Table I). Presently, she is receiving a dose of MMF 0.75 g and 0.5 g on alternate days free of symptoms. The ulcerated and erosive lesions healed completely; however, atro-
LP is an unpredictable disease with a wide range of clinical manifestations that sometimes resolve spontaneously, but may also follow a chronic, relapsing course over many years. As a result, a large variety of topical and systemic therapies is available for the treatment of LP, but there are no randomized controlled trials with definitive results.1 Current treatment modalities consist of topical and systemic corticosteroids,1,8 systemic retinoids,9,10 photochemotherapy,11 antimalarials, dapsone, and immunosuppressive agents like cyclosporine, cyclophosphamide, and azathioprine.1 Very recently, topical tacrolimus has been shown to be effective in the treatment of oral LP.12,13 MMF has been introduced into the field of dermatology for the treatment of acquired bullous autoimmune diseases, psoriasis vulgaris, and atopic eczema.2-4 Originally, because of its inhibitory effects on activated T cells, MMF was used in allogeneic renal transplantation to prolong graft survival. MMF specifically and reversibly inhibits inositolmonophosphate-dehydrogenase (IMPDH). Because lymphocytes are solely dependent on de novo nucleotide synthesis for proliferation and IMPDH is
DISCUSSION
Frieling et al 1065
J AM ACAD DERMATOL VOLUME 49, NUMBER 6
Fig 1. Case 1. A, Typical whitish Wickham’s striae on buccal mucosa before treatment with MMF. B, Complete remission after 20 weeks of treatment with MMF (2 ⫻ 1 g/d).
Fig 2. Case 2. A, Extensive disseminated lichen planus. B, Complete remission after 20 weeks of therapy with MMF (2 ⫻ 1 g/d).
one of the key enzymes for purine synthesis, MMF selectively targets activated lymphocytes.14,15 Recently, MMF has been used successfully in the therapy of chronic GVHD in patients who underwent bone marrow transplantation.6 Since GVHD shows similarities to LP and activated lymphocytes appear to play a pivotal role in the pathogenesis of both disorders,7 we initiated treatment with MMF in 3 patients with disseminated, cutaneous, or chronic, recalcitrant, mucocutaneous LP. In patients 1 and 2, disease activity was not managed by treatment with systemic or extensive use of topical corticosteroids. In these patients, MMF induced complete, long-lasting remissions and no relapses were documented over a follow-up period of up to 4 years. However, it is important to note that marked improvement of lesions only started after 4 to 6 weeks of treatment with MMF, which is apparently dependent on the mechanism of action of MMF. Patient 3 suffered from severe, erosive-ulcerative, oral and genital LP. A variety of systemic therapies failed to stop disease progression. In this recalcitrant course of the disease, the addition of MMF to the treatment regimen induced marked improvement and healing of the lesions. Two relapses after tapering off MMF clearly showed the effectiveness of MMF in this case. Our observations are supported by Nousari,16 who described a similar case of recalcitrant, bullous LP that was successfully treated with MMF.
MMF was well tolerated. None of the patients experienced any relevant short- or long-term side effects except minor gastrointestinal disturbances at the beginning of MMF treatment. In particular, we did not see an increased rate of viral or bacterial infections in our patients. Laboratory analyses recommended for immunosuppression were routinely performed and showed no abnormalities. Studies in rheumatoid arthritis have demonstrated no clinically significant nephrotoxicity, hepatotoxicity, bone marrow toxicity, or effect on blood pressure attributable to MMF.17 In comparison to other immunosuppressive drugs like cyclosporine, azathioprine, and oral corticosteroids, the side-effect profile of MMF appears to be safer. Clearly, larger multicenter investigations are required to determine the effectiveness of MMF in the treatment of severe LP compared to other immunointerventions.
CONCLUSION MMF monotherapy may be regarded safe and effective in the management of generalized, disseminated, cutaneous, and erosive mucocutaneous LP. Moreover, MMF appears to be a promising therapeutic alternative especially for those LP patients who present with refractory severe disease or contraindications to conventional therapy including immunosuppressive agents.
1066 Frieling et al
REFERENCES 1. Cribier B, Frances C, Chosidow O. Treatment of lichen planus. An evidence-based medicine analysis of efficacy. Arch Dermatol 1998;134:1521-30. 2. Bo¨hm M, Beissert S, Schwarz T, Metze D, Luger TA. Bullous pemphigoid treated with mycophenolate mofetil. Lancet 1997;349: 541. 3. Enk AH, Knop J. Treatment of pemphigus vulgaris with mycophenolate mofetil. Lancet 1997;350:494. 4. Haufs M, Beissert S, Grabbe S, Schu¨tte B, Luger TA. Psoriasis vulgaris treated successfully with mycophenolate mofetil. Br J Dermatol 1998;138:179-81. 5. Grundmann-Kollmann M, Podda M, Ochsendorf F, Boehncke WH, Kaufmann R, Zollner TM. Mycophenolate mofetil is effective in the treatment of atopic dermatitis. Arch Dermatol 2001;137: 870-3. 6. Basara N, Blau WI, Romer E, Rudolphi M, Bischof M, Kirsten D, et al. Mycophenolate mofetil for the treatment of acute and chronic GVHD in bone marrow transplant patients. Bone Marrow Transplant 1998;22:61-5. 7. Oliver GF, Winkelmann RK, Muller SA. Lichenoid dermatitis: a clinicopathologic and immunopathologic review of sixty-two cases. J Am Acad Dermatol 1989;21:284-92. 8. Lozada-Nur F, Miranda C. Oral lichen planus: topical and systemic therapy. Semin Cutan Med Surg 1997;16:295-300. 9. Laurberg G, Geiger JM, Hjorth N, Holm P, Hou-Jensen K, Jakob-
J AM ACAD DERMATOL DECEMBER 2003
10.
11.
12.
13.
14.
15. 16.
17.
sen KU, et al. Treatment of lichen planus with acitretin: a doubleblind, placebo-controlled study in 65 patients. J Am Acad Dermatol 1991;24:434-7. Gorsky M, Ravin M. Efficacy of etretinate (Tigason) in symptomatic oral lichen planus. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1992;73:52-5. Ortonne JP, Thivolet J, Sannwald C. Oral photochemotherapy in the treatment of lichen planus (LP). Clinical results, histopathology and ultrastructural observations. Br J Dermatol 1978;99:7788. Rozycki TW, Rogers RS III, Pittelkow MR, McEvoy MT, el-Azhary RA, Bruce AJ, et al. Topical tacrolimus in the treatment of symptomatic oral lichen planus: a series of 13 patients. J Am Acad Dermatol 2002;46:27-34. Kaliakatsou F, Hodgson TA, Lewsey JD, Hegarty AM, Murphy AG, Porter SR. Management of recalcitrant ulcerative oral lichen planus with topical tacrolimus. J Am Acad Dermatol 2002;46:35-41. Allision AC, Eugui EM. Purine metabolism and immunosuppressive effects of mycophenolate mofetil (MMF). Clin Transplant 1996;10:77-84. Lipsky JJ. Mycophenolate mofetil. Lancet 1996;348:1357-59. Nousari HC. Successful treatment of resistant hypertrophic and bullous lichen planus with mycophenolate mofetil. Arch Dermatol 1999;135:1420-1. Goldblum R. Therapy of rheumatoid arthritis with mycophenolate mofetil. Clin Exp Rheumatol 1993;11(Suppl 8):117-9.
Treatment of severe lichen planus with mycophenolate mofetil Uta Frieling, MD, Gisela Bonsmann, MD, Thomas Schwarz, MD, Thomas A. Luger, MD, and Stefan Beissert, MD Mu ¨ nster, Germany Lichen planus (LP) is an inflammatory skin disorder with a wide range of clinical appearances. The treatment of disseminated and especially erosive forms of LP is often difficult and disappointing. Activated T cells are important in the pathogenesis of LP as indicated by the dermal lymphocytic infiltrate leading to keratinocyte destruction and lesion formation. Similar histologic findings are present in graft-versus-host disease. Since T cells are key players in the development of both disorders and mycophenolate mofetil has been successfully introduced in the treatment of graft-versus-host disease, we have examined the therapeutic potential of this agent in 3 patients suffering from disseminated and erosive LP. Mycophenolate mofetil was well tolerated and induced complete remission in 2 patients, and substantial improvement in the third patient. (J Am Acad Dermatol 2003;49:1063-6.)
L
ichen planus (LP) is a papulosquamous inflammatory disorder, which affects the skin, mucous membranes, nails, and hair follicles. LP usually occurs as a benign disease with spontaneous remissions and exacerbations. Nonetheless, therapeutic management of extensive disseminated and especially erosive LP can be challenging and discouraging for both the patient and the physician.1 Mucocutaneous lesions that are sometimes also ulcerated cause considerable discomfort and disability. In such patients, the treatment of choice is systemic immunosuppression. However, general immunosuppression may be limited by significant adverse effects. Therefore, the development of specialized immunosuppressive regimens that are better tolerated with minimal side effects is of particular practical relevance. A few years ago, a new immunosuppressive agent, mycophenolate mofetil (MMF), which specifically and reversibly inhibits the proliferation of activated T cells, was introduced in the treatment of autoimmune and inflammatory skin disorders.2-5 Furthermore, MMF has also been successfully used From the Department of Dermatology, University of Mu¨nster. Funding sources: None. Conflict of interest: None identified. Presented in part at the meeting of the German Dermatologic Society (DDG), Berlin, May 2001. Reprint requests: Stefan Beissert, MD, Department of Dermatology, Von-Esmarch-Str. 58, D-48149 Mu¨nster, Germany. E-mail: [email protected]. Copyright © 2003 by the American Academy of Dermatology, Inc. 0190-9622/2003/$30.00 ⫹ 0 doi:10.1016/S0190-9622(03)02111-X
in the treatment of graft-versus-host disease (GVHD).6 Both GVHD and LP are characterized by activated T cells, which play a pivotal role in lesion formation.7 Thus, we have used MMF for the treatment of LP in two patients who suffered from extensive, disseminated LP and in one patient with a severe, erosive, recalcitrant, mucocutaneous form of the disease. We report on the successful use of MMF in the management of these patients’ conditions.
CASE REPORTS Cases 1 and 2 A 34-year-old white woman and a 17-year-old white male patient presented with a 2- to 3-month history of extensive generalized LP including nonpainful Wickham’s striae of the buccal mucosa. Biopsies showed changes characteristic of LP. There was worsening of the disease on treatment with systemic (20 mg/d over 2 weeks) and potent topical corticosteroids (class II and III over 5 weeks) in the woman, and with potent topical corticosteroids (class III over 6-8 weeks) in the male patient. Both patients suffered from extreme pruritus. Review of systems together with laboratory analyses including hepatitis serologies was unremarkable. After exclusion of potential underlying disease contraindicated immunosuppressive therapy (eg, tuberculosis) and informed consent had been obtained, both patients received MMF 1 g twice daily. During the first weeks of treatment there was no marked improvement of the lesions, but pruritus diminished. Within 5 to 6 weeks of treatment all papulosquamous and oral reticulated lesions started to decrease. Complete remission was achieved after approximately 20 weeks 1063
1064 Frieling et al
J AM ACAD DERMATOL DECEMBER 2003
Table I. Summary of patients and treatments LP
MMF treatment
Mucosa
Case Sex/Age No. (y)*
Skin
Oral Genital
Duration (mo)
Previous treatment
Dosage/ (g/d)
Duration (mo)
Concurrent treatment
Therapeutic effects
Follow-up (mo)
1
F/34
dLP
rLP
/
2
SC, TC
2.0
5
/
CR
19
2
M/17
dLP
rLP
/
3
TC
2.0
5
/
CR
65
3
F/54
/
eLP
eLP
65
TC, SC 2.0 Hydroxy1.0 chloroquine 0.5 Dapsone 1.5 Acitretin 1.25 1.0 Azathioprine 0.75 Pulsed 1.0 cyclo0.75 phosphamide/ dexamethasone 0.75/0.5
12 6 2 8 2 2 1 9 2 2
MI Initially pulsed cyclophosphamide/ dexamethasone (9 mo)
46; MMF cont’d
CR, Complete remission; dLP, disseminated; eLP, erosive lichen planus; MI, marked improvement; rLP, reticulated lichen planus; SC, systemic corticosteroids; TC, topical corticosteroids. *Age at onset of disease.
of treatment. Medication was discontinued, and no new lesions developed during a follow-up period of 17 and 63 months, respectively, in the female and male patient. MMF was well tolerated without any side effects.
phic scarring persisted. Therapy was tolerated well without any side effects. In summary, quality of life in this patient was markedly improved with MMF therapy.
Case 3 A 59-year-old white female patient had a 5-year history of severe recalcitrant erosive LP of the oral and genital mucous membranes. Her past medical history was uneventful and she was taking no medication before the onset of the disease. Histology demonstrated typical features of erosive LP. Hepatitis serology was negative. Previous treatment included multiple other immunomodulating and immunosuppressive therapies. Since her disease was still uncontrolled, MMF was added at a dose of 1 g twice daily to the last treatment with pulsed cyclophosphamide/dexamethasone. After 9 months of this combination therapy, erosive lesions diminished and cyclophosphamide/dexamethasone pulses were discontinued. Subsequently, the lesions cleared and MMF was quickly reduced to 0.5 g twice daily. However, during the following months, she experienced two relapses when MMF was reduced below 1 g daily. Each time, her disease stabilized with an increased dose of MMF (Table I). Presently, she is receiving a dose of MMF 0.75 g and 0.5 g on alternate days free of symptoms. The ulcerated and erosive lesions healed completely; however, atro-
LP is an unpredictable disease with a wide range of clinical manifestations that sometimes resolve spontaneously, but may also follow a chronic, relapsing course over many years. As a result, a large variety of topical and systemic therapies is available for the treatment of LP, but there are no randomized controlled trials with definitive results.1 Current treatment modalities consist of topical and systemic corticosteroids,1,8 systemic retinoids,9,10 photochemotherapy,11 antimalarials, dapsone, and immunosuppressive agents like cyclosporine, cyclophosphamide, and azathioprine.1 Very recently, topical tacrolimus has been shown to be effective in the treatment of oral LP.12,13 MMF has been introduced into the field of dermatology for the treatment of acquired bullous autoimmune diseases, psoriasis vulgaris, and atopic eczema.2-4 Originally, because of its inhibitory effects on activated T cells, MMF was used in allogeneic renal transplantation to prolong graft survival. MMF specifically and reversibly inhibits inositolmonophosphate-dehydrogenase (IMPDH). Because lymphocytes are solely dependent on de novo nucleotide synthesis for proliferation and IMPDH is
DISCUSSION
Frieling et al 1065
J AM ACAD DERMATOL VOLUME 49, NUMBER 6
Fig 1. Case 1. A, Typical whitish Wickham’s striae on buccal mucosa before treatment with MMF. B, Complete remission after 20 weeks of treatment with MMF (2 ⫻ 1 g/d).
Fig 2. Case 2. A, Extensive disseminated lichen planus. B, Complete remission after 20 weeks of therapy with MMF (2 ⫻ 1 g/d).
one of the key enzymes for purine synthesis, MMF selectively targets activated lymphocytes.14,15 Recently, MMF has been used successfully in the therapy of chronic GVHD in patients who underwent bone marrow transplantation.6 Since GVHD shows similarities to LP and activated lymphocytes appear to play a pivotal role in the pathogenesis of both disorders,7 we initiated treatment with MMF in 3 patients with disseminated, cutaneous, or chronic, recalcitrant, mucocutaneous LP. In patients 1 and 2, disease activity was not managed by treatment with systemic or extensive use of topical corticosteroids. In these patients, MMF induced complete, long-lasting remissions and no relapses were documented over a follow-up period of up to 4 years. However, it is important to note that marked improvement of lesions only started after 4 to 6 weeks of treatment with MMF, which is apparently dependent on the mechanism of action of MMF. Patient 3 suffered from severe, erosive-ulcerative, oral and genital LP. A variety of systemic therapies failed to stop disease progression. In this recalcitrant course of the disease, the addition of MMF to the treatment regimen induced marked improvement and healing of the lesions. Two relapses after tapering off MMF clearly showed the effectiveness of MMF in this case. Our observations are supported by Nousari,16 who described a similar case of recalcitrant, bullous LP that was successfully treated with MMF.
MMF was well tolerated. None of the patients experienced any relevant short- or long-term side effects except minor gastrointestinal disturbances at the beginning of MMF treatment. In particular, we did not see an increased rate of viral or bacterial infections in our patients. Laboratory analyses recommended for immunosuppression were routinely performed and showed no abnormalities. Studies in rheumatoid arthritis have demonstrated no clinically significant nephrotoxicity, hepatotoxicity, bone marrow toxicity, or effect on blood pressure attributable to MMF.17 In comparison to other immunosuppressive drugs like cyclosporine, azathioprine, and oral corticosteroids, the side-effect profile of MMF appears to be safer. Clearly, larger multicenter investigations are required to determine the effectiveness of MMF in the treatment of severe LP compared to other immunointerventions.
CONCLUSION MMF monotherapy may be regarded safe and effective in the management of generalized, disseminated, cutaneous, and erosive mucocutaneous LP. Moreover, MMF appears to be a promising therapeutic alternative especially for those LP patients who present with refractory severe disease or contraindications to conventional therapy including immunosuppressive agents.
1066 Frieling et al
REFERENCES 1. Cribier B, Frances C, Chosidow O. Treatment of lichen planus. An evidence-based medicine analysis of efficacy. Arch Dermatol 1998;134:1521-30. 2. Bo¨hm M, Beissert S, Schwarz T, Metze D, Luger TA. Bullous pemphigoid treated with mycophenolate mofetil. Lancet 1997;349: 541. 3. Enk AH, Knop J. Treatment of pemphigus vulgaris with mycophenolate mofetil. Lancet 1997;350:494. 4. Haufs M, Beissert S, Grabbe S, Schu¨tte B, Luger TA. Psoriasis vulgaris treated successfully with mycophenolate mofetil. Br J Dermatol 1998;138:179-81. 5. Grundmann-Kollmann M, Podda M, Ochsendorf F, Boehncke WH, Kaufmann R, Zollner TM. Mycophenolate mofetil is effective in the treatment of atopic dermatitis. Arch Dermatol 2001;137: 870-3. 6. Basara N, Blau WI, Romer E, Rudolphi M, Bischof M, Kirsten D, et al. Mycophenolate mofetil for the treatment of acute and chronic GVHD in bone marrow transplant patients. Bone Marrow Transplant 1998;22:61-5. 7. Oliver GF, Winkelmann RK, Muller SA. Lichenoid dermatitis: a clinicopathologic and immunopathologic review of sixty-two cases. J Am Acad Dermatol 1989;21:284-92. 8. Lozada-Nur F, Miranda C. Oral lichen planus: topical and systemic therapy. Semin Cutan Med Surg 1997;16:295-300. 9. Laurberg G, Geiger JM, Hjorth N, Holm P, Hou-Jensen K, Jakob-
J AM ACAD DERMATOL DECEMBER 2003
10.
11.
12.
13.
14.
15. 16.
17.
sen KU, et al. Treatment of lichen planus with acitretin: a doubleblind, placebo-controlled study in 65 patients. J Am Acad Dermatol 1991;24:434-7. Gorsky M, Ravin M. Efficacy of etretinate (Tigason) in symptomatic oral lichen planus. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1992;73:52-5. Ortonne JP, Thivolet J, Sannwald C. Oral photochemotherapy in the treatment of lichen planus (LP). Clinical results, histopathology and ultrastructural observations. Br J Dermatol 1978;99:7788. Rozycki TW, Rogers RS III, Pittelkow MR, McEvoy MT, el-Azhary RA, Bruce AJ, et al. Topical tacrolimus in the treatment of symptomatic oral lichen planus: a series of 13 patients. J Am Acad Dermatol 2002;46:27-34. Kaliakatsou F, Hodgson TA, Lewsey JD, Hegarty AM, Murphy AG, Porter SR. Management of recalcitrant ulcerative oral lichen planus with topical tacrolimus. J Am Acad Dermatol 2002;46:35-41. Allision AC, Eugui EM. Purine metabolism and immunosuppressive effects of mycophenolate mofetil (MMF). Clin Transplant 1996;10:77-84. Lipsky JJ. Mycophenolate mofetil. Lancet 1996;348:1357-59. Nousari HC. Successful treatment of resistant hypertrophic and bullous lichen planus with mycophenolate mofetil. Arch Dermatol 1999;135:1420-1. Goldblum R. Therapy of rheumatoid arthritis with mycophenolate mofetil. Clin Exp Rheumatol 1993;11(Suppl 8):117-9.