852
Journal of the American Academy of Dermatology
Briefcommunications
Efficacy of acitretin in severe cutaneous lichen planus P. A. Viglioglia, MD,a C. R. Villanueva, MD,a A. D. Martorano, MD,a A. M. Cahuepe, MD,a c. A. Traballi, MD,b and J.-M. Geiger, MDc Buenos Aires.
Argentina, and Basel, Switzerland The aromatic retinoid acitretin (previously designated Ro 10-1670, etretin) is the main metabolite of etretinate (Tigason, Europe, Tegison. U.S.A.)l,2 Acitretin is characterized pharmacologically by a lower lipophilicity, lack of storage in the body, and more rapid clearance and elimination (elimination half-life, 50 hours), when compared with etretinate (elimination half-life, 100 days)2-4. Acitretin has been shown to be as effective as etretinate in the treatment of skin diseases with abnormal keratiniZation. 5-7 We investigated the effect of acitretin in patients with severe forms of lichen planus.
From the Dermatology Service, Hospitalde Agudos Juan A. Fermindez," the Departmentof International Clinical Research, Productos Roche Sociedad Anonirna Quimicae Industrial, Buenos Aires," and theDepartmentofClinical Research Dermatology, F. Hoffmann-La Roche & Co. Ltd., Basel," Reprintrequests: Pablo A. Viglioglia, MD, Servicio de Derrnatologia, Hospital de Agudos Juan A. Fernandez, Cerviiio 3356,1425 Buenos Aires, Argentina. 16/4/16438
Patients and methods. Eleven outpatients, six men and five women (mean age 38.5 years), were included in this study. Ten patients had typical lichen planus and one had the actinic type. The disease had been present 49 days on average (range 10 to 180days). Acitretin was administered at a dosage of 30 mg/day for 8 weeks, followed by another 8-week treatment with the dosage individually adjusted to obtain improvement while minimizing side effects. Clinical efficacy and severity and extent of the lesions were evaluated at each visit. Pruritus, papules, erythema, and vesiclesor bullae were rated according to the following scale: 3 = severe, 2 = moderate, 1 = slight, 0 = absent. At the same intervals side effects were recorded. Before therapy was begun, at the fourth week, and after 16 weeks of treatment, the following laboratory studies were obtained: counts for RBCs, WBC~, and thrombocytes; levelsof bilirubin, creatinine, uric acid, glucose, alkaline phosphatase, aspartate aminotransferase (SOOT), and alanine aminotransferase (SGPT); and values of cholesterol and triglycerides. The last four determinations were also checked after 4 and 12 weeksof therapy. Women of childbearing potential were instructed to use a reliable contraceptive measure, Nine patients had been treated previously with several topical and systemic preparations with poor to moderate response. Results. Three patients did not complete the 16-week treatment; one patient did not return after the 8-week visit and acitretin administration had to be stopped in two patients because of severe adverse reactions. The clinical results are shown in Table I. The severity of the clinical manifestations diminished significantly after 4 weeks of therapy and the improvement stabilized thereafter. The
Table I. Change in severity and extent of lichen planus lesions during acitretin treatment Week of therapy
Symptom/sign
Pruritus
Erythema
Papulosis
Vesiclesjbullae
Degree of severity
None Slight Moderate Severe None Slight Moderate Severe
n. Number of patients.
16 (n=8)
5
4 5 0
7
3 2
0
0
0
3 5 2 1 3
4 5
4 4
1 0
1 0
6
4 4 1 0 9 0
8
(n = 11)
1
3
5
1 5 4 0
3
2 8 1
None Slight Moderate Severe
0 3 6
None Slight Moderate Severe
9 0 1 1
Mean percent body surface
12 (n=9)
4
Before therapy (n = 11)
2
45%
5
3 0 11 0
I
(n=10)
4 0 0
10
0
0 0
0 40%
I
1 0
0 4 2 2 0
5 2 1
0
7 1
0
0
0
0
0
26%
17%
7%
Volume 22 Number 5, Part I May 1990
extent of involvement also decreased progressively during treatment. Complete remission or marked improvement was obtained in six of eight patients who completed the study. No significant changes in laboratory values were detected. During the second treatment phase (weeks 9 to 16) the dosage of 30 tiig] day was maintained in four patients and decreased to 20 or 10 mg/day in the other four. Comment The results obtained in this open study demonstrate that acitretin is effective in the treatment of severe lichen planus. The rapid improvement suggests that acitretin may be slightly more effective than etretinate or isotretinoin. An initial dosage of acitretin, 30 mg/ day, gave good results, similar to those observed after 1 mg/kg/day (50 to 100 tag] day) of either etretinate8. 1! or isotretinoin.P The side effects were those commonly seen with etretinate.P The main advantage of acitretin over etretinate is its more rapid elimination. Thus the teratogenic risk is essentially limited to the treatment period.
Brief communications 853 Familial nevus sebaceus of J adassolm: Occurrence in three generations William J. SaW, Jr., MD Oklahoma City, Oklahoma Until recently the appearance of nevus sebaceus was thought to be sporadic and not inherited. 1 This is the second reported case of inherited nevus sebaceus and the first to occur in three generations. Case report. A 65-year-old black man had a lifelong history of a 4 X6 em bald area on the crown of the scalp. Within the bald spot a 2.5 X 3.5 em tumor had grown From the Department of Dermatology, University of Oklahoma Health Sciences Center. Reprint requests: William J. Sahl, Jr., MD, Chief, Dermatologic Surgery, Department of Dermatology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104.
16/4/16080
REFERENCES 1. Haenni R. Pharmacokinetic and metabolic pathways of
2.
3.
4.
5.
6.
7.
8. 9.
10.
11.
12.
systematically applied retinoids. Dermatologica 1978; 157(suppl 1):5-10. Paravicini V, Stoeckel K, McNamara PJ, et al. On metabolism and pharmacokinetics of an aromatic retinoid. Ann NY Acad Sci 1981;359:54-67. Paravicini V, Camenzind M, Gower M, et al. Multiple dose pharmacokinetics of Ro 10-1670, the main metabolite of etretinate (Tigason). In: Saurat H-H, ed. Retinoids: new trends in research and therapy. Basel, Switzerland; Karger, 1985:289-92. Brindley C. An overview of recent clinical pharmacokinetic studies with acitretin (Ro 10-1670, etretin). Dermatologica 1989;178:79-87. Geiger J-M, Ott F, Bollag W. Clinical evaluation of an aromatic retinoid, Ro 10-1670, in severe psoriasis. Curr Ther Res 1984;35:735-40. Geiger J-M, Czarnetzki B-M. Acitretin (Ro 10-1670, etretin): overall evaluation of clinical studies. Dermatologica 1988;176:182-90. Goldfarb M, Ellis C, Gupta A, et al. Acitretin improves psoriasis in a dose-dependent fashion. JAM ACAD DERMATOL 1988;18:655-62. Schuppli R. The efficacy of a new retinoid (Ro 10-9359) in lichen planus. Dermatologica 1978;157(suppll):60-3. Ebner H. Erfahrungen mit der systemischen Retinoidbehandlung (Ro 10-9359) bei Lichen rubber planus. Wien Klin Wochenschr 1979;91:161-4. Viglioglia PA. Therapeutic evaluation of the oral retinoid Ro 10-9359 in several non-psoriatic dermatoses. Br J Dermatol 1980;103:483-7. Cordero AA, Allevato MAJ, Barclay CA, et al. Treatment of lichen planus and leukoplakia with the oral retinoid Ro 10-9359. In: Orfanos CE, Braun-Falco 0, Farber EM, et al., eds. Retinoids: advances in basic research and therapy. Berlin: Springer, 1981:273-8. Ellis CN, Voorhees JJ. Etretinate therapy. J AM ACAD DERMATOL 1987;16:267-91.
2 Fig. 1. Photomicrograph of basal cell carcinoma arising within index patient's nevus sebaceus. (Hematoxylineosin stain; X32.) Fig. 2. Photomicrograph of index patient's nevus sebaceus after excision of basal cell carcinoma. (Hematoxylin-eosin stain; X28.)
Journal of the American Academy of Dermatology
Briefcommunications
Efficacy of acitretin in severe cutaneous lichen planus P. A. Viglioglia, MD,a C. R. Villanueva, MD,a A. D. Martorano, MD,a A. M. Cahuepe, MD,a c. A. Traballi, MD,b and J.-M. Geiger, MDc Buenos Aires.
Argentina, and Basel, Switzerland The aromatic retinoid acitretin (previously designated Ro 10-1670, etretin) is the main metabolite of etretinate (Tigason, Europe, Tegison. U.S.A.)l,2 Acitretin is characterized pharmacologically by a lower lipophilicity, lack of storage in the body, and more rapid clearance and elimination (elimination half-life, 50 hours), when compared with etretinate (elimination half-life, 100 days)2-4. Acitretin has been shown to be as effective as etretinate in the treatment of skin diseases with abnormal keratiniZation. 5-7 We investigated the effect of acitretin in patients with severe forms of lichen planus.
From the Dermatology Service, Hospitalde Agudos Juan A. Fermindez," the Departmentof International Clinical Research, Productos Roche Sociedad Anonirna Quimicae Industrial, Buenos Aires," and theDepartmentofClinical Research Dermatology, F. Hoffmann-La Roche & Co. Ltd., Basel," Reprintrequests: Pablo A. Viglioglia, MD, Servicio de Derrnatologia, Hospital de Agudos Juan A. Fernandez, Cerviiio 3356,1425 Buenos Aires, Argentina. 16/4/16438
Patients and methods. Eleven outpatients, six men and five women (mean age 38.5 years), were included in this study. Ten patients had typical lichen planus and one had the actinic type. The disease had been present 49 days on average (range 10 to 180days). Acitretin was administered at a dosage of 30 mg/day for 8 weeks, followed by another 8-week treatment with the dosage individually adjusted to obtain improvement while minimizing side effects. Clinical efficacy and severity and extent of the lesions were evaluated at each visit. Pruritus, papules, erythema, and vesiclesor bullae were rated according to the following scale: 3 = severe, 2 = moderate, 1 = slight, 0 = absent. At the same intervals side effects were recorded. Before therapy was begun, at the fourth week, and after 16 weeks of treatment, the following laboratory studies were obtained: counts for RBCs, WBC~, and thrombocytes; levelsof bilirubin, creatinine, uric acid, glucose, alkaline phosphatase, aspartate aminotransferase (SOOT), and alanine aminotransferase (SGPT); and values of cholesterol and triglycerides. The last four determinations were also checked after 4 and 12 weeksof therapy. Women of childbearing potential were instructed to use a reliable contraceptive measure, Nine patients had been treated previously with several topical and systemic preparations with poor to moderate response. Results. Three patients did not complete the 16-week treatment; one patient did not return after the 8-week visit and acitretin administration had to be stopped in two patients because of severe adverse reactions. The clinical results are shown in Table I. The severity of the clinical manifestations diminished significantly after 4 weeks of therapy and the improvement stabilized thereafter. The
Table I. Change in severity and extent of lichen planus lesions during acitretin treatment Week of therapy
Symptom/sign
Pruritus
Erythema
Papulosis
Vesiclesjbullae
Degree of severity
None Slight Moderate Severe None Slight Moderate Severe
n. Number of patients.
16 (n=8)
5
4 5 0
7
3 2
0
0
0
3 5 2 1 3
4 5
4 4
1 0
1 0
6
4 4 1 0 9 0
8
(n = 11)
1
3
5
1 5 4 0
3
2 8 1
None Slight Moderate Severe
0 3 6
None Slight Moderate Severe
9 0 1 1
Mean percent body surface
12 (n=9)
4
Before therapy (n = 11)
2
45%
5
3 0 11 0
I
(n=10)
4 0 0
10
0
0 0
0 40%
I
1 0
0 4 2 2 0
5 2 1
0
7 1
0
0
0
0
0
26%
17%
7%
Volume 22 Number 5, Part I May 1990
extent of involvement also decreased progressively during treatment. Complete remission or marked improvement was obtained in six of eight patients who completed the study. No significant changes in laboratory values were detected. During the second treatment phase (weeks 9 to 16) the dosage of 30 tiig] day was maintained in four patients and decreased to 20 or 10 mg/day in the other four. Comment The results obtained in this open study demonstrate that acitretin is effective in the treatment of severe lichen planus. The rapid improvement suggests that acitretin may be slightly more effective than etretinate or isotretinoin. An initial dosage of acitretin, 30 mg/ day, gave good results, similar to those observed after 1 mg/kg/day (50 to 100 tag] day) of either etretinate8. 1! or isotretinoin.P The side effects were those commonly seen with etretinate.P The main advantage of acitretin over etretinate is its more rapid elimination. Thus the teratogenic risk is essentially limited to the treatment period.
Brief communications 853 Familial nevus sebaceus of J adassolm: Occurrence in three generations William J. SaW, Jr., MD Oklahoma City, Oklahoma Until recently the appearance of nevus sebaceus was thought to be sporadic and not inherited. 1 This is the second reported case of inherited nevus sebaceus and the first to occur in three generations. Case report. A 65-year-old black man had a lifelong history of a 4 X6 em bald area on the crown of the scalp. Within the bald spot a 2.5 X 3.5 em tumor had grown From the Department of Dermatology, University of Oklahoma Health Sciences Center. Reprint requests: William J. Sahl, Jr., MD, Chief, Dermatologic Surgery, Department of Dermatology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104.
16/4/16080
REFERENCES 1. Haenni R. Pharmacokinetic and metabolic pathways of
2.
3.
4.
5.
6.
7.
8. 9.
10.
11.
12.
systematically applied retinoids. Dermatologica 1978; 157(suppl 1):5-10. Paravicini V, Stoeckel K, McNamara PJ, et al. On metabolism and pharmacokinetics of an aromatic retinoid. Ann NY Acad Sci 1981;359:54-67. Paravicini V, Camenzind M, Gower M, et al. Multiple dose pharmacokinetics of Ro 10-1670, the main metabolite of etretinate (Tigason). In: Saurat H-H, ed. Retinoids: new trends in research and therapy. Basel, Switzerland; Karger, 1985:289-92. Brindley C. An overview of recent clinical pharmacokinetic studies with acitretin (Ro 10-1670, etretin). Dermatologica 1989;178:79-87. Geiger J-M, Ott F, Bollag W. Clinical evaluation of an aromatic retinoid, Ro 10-1670, in severe psoriasis. Curr Ther Res 1984;35:735-40. Geiger J-M, Czarnetzki B-M. Acitretin (Ro 10-1670, etretin): overall evaluation of clinical studies. Dermatologica 1988;176:182-90. Goldfarb M, Ellis C, Gupta A, et al. Acitretin improves psoriasis in a dose-dependent fashion. JAM ACAD DERMATOL 1988;18:655-62. Schuppli R. The efficacy of a new retinoid (Ro 10-9359) in lichen planus. Dermatologica 1978;157(suppll):60-3. Ebner H. Erfahrungen mit der systemischen Retinoidbehandlung (Ro 10-9359) bei Lichen rubber planus. Wien Klin Wochenschr 1979;91:161-4. Viglioglia PA. Therapeutic evaluation of the oral retinoid Ro 10-9359 in several non-psoriatic dermatoses. Br J Dermatol 1980;103:483-7. Cordero AA, Allevato MAJ, Barclay CA, et al. Treatment of lichen planus and leukoplakia with the oral retinoid Ro 10-9359. In: Orfanos CE, Braun-Falco 0, Farber EM, et al., eds. Retinoids: advances in basic research and therapy. Berlin: Springer, 1981:273-8. Ellis CN, Voorhees JJ. Etretinate therapy. J AM ACAD DERMATOL 1987;16:267-91.
2 Fig. 1. Photomicrograph of basal cell carcinoma arising within index patient's nevus sebaceus. (Hematoxylineosin stain; X32.) Fig. 2. Photomicrograph of index patient's nevus sebaceus after excision of basal cell carcinoma. (Hematoxylin-eosin stain; X28.)
