cutaneous melanomas in patients treated with psoralens plus ultraviolet a

I III I III II IIIII 11 II II IIIII

Cutaneous melanomas in patients with psoralens plus ultraviolet A

treated

A case report and the experience of the PUVA Follow-up Study

Aditya K. Gupta, M.D.,* Robert S. Stem, M.D.,** Neil A. Swanson, M.D.,* Thomas F. Anderson, M.D.,* and the PUVA Follow-Up Study*** Ann Arbor, MI, and Boston, MA

Psoralens plus ultraviolet A (PUVA) therapy is widely used in the treatment o f psoriasis and other cutaneous conditions. We present the case of a patient who developed a superficial spreading melanoma 3 years after first being treated with PUVA. The development of melanomas in patients receiving PUVA is reviewed. During 13,224 person-years of prospective follow-up of 1380 patients enrolled in the PUVA follow-up study, three melanomas were diagnosed, which does not differ significantly from the expected rate (relative risk = 1.5 with 90% confidence interval 0.3 to 7.3). However, considering the effects of PUVA on melanocytes and that the development of melanomas may have a long latent period, continued follow-up studies are indicated. (J AM ACAD DERMATOL 1988;19:67-76.)

The combination of psoralens plus ultraviolet A (PUVA) was approved for the management of se-

From the Department of Dermatology, University of Michigan, Ann Arbor,* and the Department of Dermatology (Beth Israel Hospital), Harvard Medical School, Boston,** and 15 other centers.***

Supported in part by the Babcock Foundation. Accepted for publication Dec. 18, 1987. Reprint requests to: Dr. T. F. Anderson, Department of Dermatology,

Veterans Administration Medical Center, Ann Arbor, MI 48105, ***Centers participating: University of Michigan Medical School

(J. Voorhees, M.D.); Massachusetts General Hospital (T. B. Fitz- patrick, M.D,, and E. Gonzalez, M.D.); Beth Israel Hospital (K. Arndt, M.D.); Stanford University School of Medicine (E. Abel, M.D.); University of California Medical School, San Fran- cisco (B. Wintroub, M.D., and J. H. Epstein, M.D.); Baylor College of Medicine (J. Wolf, M.D.); Washington Hospital Center (T. P. Nigra, M.D.); Columbia University College of Physicians and Surgeons (R. Armstrong, M.D., and L. Harber, M.D.); Mayo Graduate School of Medicine (S. Muller, M.D.); University of Miami (J. R. Taylor, M.D.); Mr. Sinai Medical Center (P. Frost, M.D., and S.N. Horwitz, M.D.); Temple University School of Medicine (F. Urbach, M.D.); Yale University School of Medicine (I. M. Braverman, M.D.); Duke University Medical Center (J. Murray, M.D.); University of Pennsylvania Hospitals (J. Petrozzi, M.D.); and Dartmouth Medical School (R. D. Baughman, M.D.)

vere psoriasis by the Food and Drug Administra- tion in 1982.1 Since its introduction in 1974, 2 PUVA therapy has been an effective treatment mo- dality in many cutaneous conditions. Its short-term side effects are generally well known. Long-term and dose-dependent side effects include an increased risk of developing accelerated skin aging, 3 actinic keratosis,4 squamous cell carcinoma, 1 atypical cutaneous pigmentation, 5 PUVA lentigo, 6 and ophthalmologic abnormalities. 7 Concem has been expressed that PUVA might also increase the risk of melanoma.

We report the development of a superficial spreading melanoma in a patient who received PUVA therapy and review the PUVA Follow-Up Study's experience with melanoma and other reported cases in whom melanomas developed at some time after PUVA therapy. In 1975 and 1976 1380 patients at 16 university centers were enrolled in the PUVA Follow-Up Study, the methods of which have been reported. 8 We have used Miet- tinen's method 9 to calculate significance and confidence intervals for PUVA study population data.

67

6 8 Gupta et al. Journal of the

American Academy of Dermatology

T a b l e I . Melanomas that have developed in patients treated with PUVA

. . . . . . . . I Age(r;); I ] . . . .

. . . . . . . Previous treatments Author(s) [ sex/race Occupation . . . .

Forrest and Forest I~ 30 /M/W NR None (U.S.A.) 1980

Previous history of skin cancer

NR

Frenk H (Switzer- 37 /F /W NR 1960; Arsenic; land) 1983 1963, Grenz ray,

single doses of 120-180 reads (total dose not known); 1976, PUVA; 1978, PUVA combined with etretinate (doses of UVA not reported)

Marx et al. 12 34 /M/W NR Tar, anthralin, UVA, (U.S.A.) 1983 topical steroids, Case 1 Grenz ray to

scalp; no arsenic or methotrexate

Case 2 50 /F /W NR Tar, UVA; methotrexate; no arsenic or x-ray therapy

NR

No

NR

AK, Actinic keratoses; AIR, not reported; SSM, superficial spreading melanoma.

CASE R E P O R T

A 51-year-old white man, skin type I, had psoriasis for 36 years. Past treatment for psoriasis included tar, anthralin, and topical corticosteroids. The patient had also taken methotrexate for 6 months in 1976. He had never received other cytotoxic agents, isotretinoin, arsenic, or x-ray therapy.

In June 1978 he began PUVA therapy with a standard oral 8-methoxypsoralen dosage of 50 mg (0.6 gm/kg body weight) and a starting ultraviolet A (UVA) dose of 0.5 J /cmL He was treated twice weekly with an incremental dose of 0.5 to 1 J /cm 2 depending on the erythema response. The patient's psoriasis responded well to treatment. After 11 treatments (38.5 J/cm 2) the patient had <5% total body surface area involvement. He then began maintenance therapy, with dosing initially once weekly and then every other week.

In 1979 after 40 treatments (149 J/cm2), the patient had <1% total body surface area and PUVA therapy

was discontinued. The patient had been a truck driver in the past and had worked outdoors, sometimes without wearing sunscreens. He was otherwise well and was taking no systemic medications. There was no evidence or past or family history of previous cutaneous cancers, dysplastic nevi, or melanoma.

In May 1981 the patient first noticed a brown macule on his right arm just proximal to the elbow. The lesion was approximately 1 x4 cm in size. Punch biopsy re- vealed a superficial spreading melanoma in a very early vertical growth phase. The depth of infiltration was 0.1 to 0.2 mm (level II infiltration). Subsequently a wider excision was performed. The excision margins were negative for residual melanoma. There was no lymph- adenopathy and no evidence on physical examination of spread of tumor. The complete blood count, liver function test results, and chest x-ray film were all normal.

The patient remained in good health, with no evi-

Volume 19 Number 1, Part 1 July 1988

Melanomas in patients treated with PUVA 69

Reason for receiving PUVA Therapy

Vitiligo

Pustular psoriasis

No. of Response PUVA treatments to PUVA Side effects

Started trioxalen, NR NR 10 mg po; lesion noted during third week of treatment

March 1976-Septem- NR Good ber 1982; total UVA dose 4453 J/cm z

NR

Numerous stellate, freckle-like hy- Ix)pigmented macules

Psoriasis

Psoriasis

Started August 1976, discontinued March 1980; total UVA dose 324.5 J/cm 2

Started October 1976, discontinued No- vember 1980; total UVA dose 2802 J/cm 2

66 Good NR

NR Good NR

dence of recurrence of melanoma at periodic physical examinations. His psoriasis was treated with corticosteroids, tar, and anthralin.

In July 1985 the patient was found to have a brown macule on his right shoulder. A biopsy of this lesion was initially diagnosed by an outside pathologist as lentigo maligna melanoma. A wide excision was performed. The margins were free of atypical melanocytes. There was no clinical or laboratory evidence of distant spread or of other atypical lesions. The biopsy specimen was subsequently reviewed by a panel of dermatopathologists, who concluded that this was a lentiginous junctional nevus.

RESULTS

In addition to the case we report and the three cases observed in the PUVA cohort, we are aware o f eight other reported cases of melanoma in per- sons who have been treated with PUVA therapy (Table I). 10-1s

continued

Up to September 1986, 13,224 person-years of follow-up have been completed in the PUVA follow-up study of 1380 patients. Based on Sur- veillance, Epidemiology, and End-Result incidence data, ~6 we calculate that this cohort would be expected to develop 2.05 melanomas. Three patients were found to have melanomas after the start o f PUVA therapy. In one the lesion was detected 21 months after the first treatment and after only 55 treatments. The other melanomas were detected 79 and 116 months after the first treatment; these two patients had received 284 and 46 PUVA treatments, respectively, before tumor de- tection. The relative risk for development of melanoma in the PUVA cohort is 1.46 (90% confidence interval 0.3 to 7.3). Thus in this group the risk o f melanoma is neither substantially nor significantly elevated.

Henseler et al. J7 reported on the development of

70 Gupta et al. Journal of the


Table I. Cont'd

Author(s) I Age (yr)/ sex/race

Forrest and Forest m 30/M/W (U.S.A.) 1980

Type of melanoma

Family history of melanoma/dysplastic nevus

Type of treatment given for melanoma

SSM level Ill, depth 0.32 mm

NR Wide excision

Frenk tt (Switzer- 37/F/W SSM, depth 0.51 land) 1983 mm

NR Excision

Marx et al. '2 (U.S.A.) 1983 Case 1

34/M/W

Case 2 50/F/W

SSM level I in as- sociation with in- tradermal nevus

November I980, macular uni- formly brown lesion noted on lower lip: malignant melanoma in situ

NR

NR

Excisional biopsy; later wide reexcision, no residual tumor found

Excision followed by wide reexcision, atypical melanocytes at surgical margins; second reexcision, surgical margins free of tumor and atypical melanocytes

skin tumors in the European PUVA study in 1643 patients with psoriasis who were followed for eight years. This study began in 1975 in 11 European countries (18 centers) and data obtained up to Jan- uary 1986 were reported. Only one patient developed a malignant melanoma. ~

DISCUSSION

Skin types in six of eleven patients who developed melanoma were reported (Table I). One patient had skin type I, three were of skin type II, and two had skin type III. Eight of the 10 patients (80%) whose details axe known developed a superficial spreading melanoma. ~0-~5 One patient de-

veloped a nodular melanoma. 14 In the general population the frequency of superficial spreading melanoma and nodular melanoma is 70% and 16%, respectively. ~8 From analysis of the reported cases, no clear pattern develops in the type of melanoma, cumulative UVA dosage, or time elapsed since beginning PUVA therapy before melanoma is detected.

The development of melanoma after PUVA therapy may have been coincidental. In one patienP ~ the melanoma was noted 3 weeks after the start of PUVA therapy. This is unlikely to have been a result of PUVA therapy. Other patients have been reported to have had treatments such as arsenic, ~

Volume 19 N u m b e r 1, Par t 1 July 1988

Melanomas in patients treated with PUVA '71

Results of treatment of sk in cancer Skin type

At 14 mo after NR excision, no local or distal recurrence

NR Green-brown eyes, blond hair

Follow-up 1 yr later, no recurrence

I1

N R II

conthmed

x-ray therapy, T M and methotrexate. ~2 It is not known whether these factors might predispose patients to the development of melanomas.

In some of the patients reported to have developed melanoma while receiving PUVA therapy, there is no consistent classification of melanomas. For example, in the two cases reported by Marx et al. ~ the terms malignant melanoma in situ and atypical melanocytic hyperplasia were used inter- changeably.

To determine accurately the risk of development of melanoma in patients who receive PUVA therapy, it is important to know both the at-risk population (that is, the number of recipients of PUVA)

and the number of melanomas that develop at various times after the start of therapy. Because there is no policy requiring all providers of PUVA therapy to report observed adverse effects in patients who receive PUVA, case reports are most likely to come from university centers, thus leading to a possible underreporting of melanoma cases. Also, without a consistent nomenclature for melanomas, there may be a bias in the number of cases reported. Thus in the United States the most feasible method of addressing this problem is the continued surveillance of the PUVA cohort, which has now been followed for more than a decade. In cases of uncertain pathologic diagnosis, the material could be reviewed by a central panel of dermatopathologists. In our patient the lesion was initially reported as lentigo maligna melanoma and was treated as such. However, subsequent review by a panel of dermatopathologists concluded that the lesion was a lentiginous junctional nevus.

There are various reasons for concern with PUVA therapy. PUVA therapy can be mutagenic ~9 in microorganisms and in cultured mammalian cells. The cumulative PUVA dose is positively associated with the risk of nonmelanoma cutaneous cancers, particularly squamous cell carcinomas. Predisposing risk factors for the development of nonmelanoma skin cancer may include a history of ionizing radiation, ingestion of arsenic, and a previous cutaneous malignancy. It is not known whether these could be predisposing factors for the development of naelanomas. PUVA therapy can cause various immunologic alterations. 2~ These PUVA-induced changes in immunologic function may affect the body's ability to reject ultraviolet- induced cutaneous neoplasms including, perhaps, melanomas.

In addition to keratinocytes and immune cells, PUVA is known to affect melanocytes. Patients receiving PUVA therapy often develop lentigines.2~ These are related to the number of treatments received and the dosage of UVA radiation. The histologic and ultrastructural changes seen in PUVA-induced lentigines compared with lentigines caused by the sun and light-protected buttock skin include an increased number and size of



T a b l e I. Cont'd

Age (yr)/ I Author(s) sex/race I

Johnson .3 (Nor- 22/F/W way) 1984

Occupation Previous treatments Previous history

of skin cancer

NR NR

Kemmett et al. ~4 61/M/W Clerk (U.K.) 1984

Tar, anthralin, topi- NR cal steroids

Binet et al, ~5 76/MINR NR (France) 1985

PUVA follow-up study (U.S.A.) Case 1 51/M/W Sales

representative

Goeckerman, kera- NR tolytics, steroids

No history of ioniz- No ing radiation

Case 2 67/F/W School teacher Grenz ray No

Case 3 53/M/W School teacher No history of ioniz- No ing radiation

Present case 61/M/W Truck driver (U.S.A.)

Tar, anthralin, topi- No cal steroids

melanosomes and melanocytes, increase in mel- anogenesis and clustering of melanocytes, 2a bi- nucleated melanocytes with nuclear hyperchro- matism, and cellular pleomorphism, s,6a2 Abel et al. s found melanocytic atypia consisting of large or angular hyperchromatic nuclei in 57% of PUVA-induced lentigines, 70% of nonlesional PUVA-exposed skin, and infrequently in sun-

induced lentigines. Concern has been expressed that these atypical changes could be the precursors of melanocytic dysplasia or malignancy. 5

There is probably an increased risk for melanoma in patients who have had frequent sunburns early in life and in those who bum easily and tan poorly? 3 Other risk factors for melanoma include a family history of melanoma or dysplastic nevi,



Reason for receiving PUVA

Pustular psoriasis

Therapy No. of ---] Response

PUVA treatments / to PUVA Side effects

Started December 1982, discontinued March 1983; local application of 8-methoxypsoralen

NR NR May 1983, macule noted on left hand: junctional nevus

Psoriasis

Psoriasis

Started March 1979, 184 Good discontinued Febru- ary 1983, total UVA dose 419 J/em2; PUVA reintroduced October 1983, discontinued December 1983, further UVA dose 36.5 J/cm 2

Started 1975, discon- NR Good tinued May 1983

February 1983, SSC x 2, AK x 1, lentigines, Bowen's dis- ease; August 1983, SSC, AK x3

Keratoses on trunk 1981, 1982

Psoriasis Started November 1975; 116 mo from first treatment to diagnosis

Psoriasis Started February 1976; 21 mo from first treatment to biopsy

Psoriasis Started April 1975; 79 mo from first treatment to diagnosis

Psoriasis Started June 1978, discontinued De- cember 1980; total UVA dose 149 J/cm 2

46 Good None

55 Good None

284 Good None

40 Good None

continued

preexisting congenital nevus or dysplastic nevus, increased exposure to ultraviolet light radiation, and very light-colored skin. ~4,2~

Despite the effects of PUVA on melanocytes and the carcinogenic (or immunosuppressive) effects on the development of epithelial carcinomas, it is reassuring that thus far the number of melanomas reported is not significantly greater than would be

expected in the general population. However, the development of melanoma may have a long latent period, and continued long-term follow-up of a well-defined cohort of the patients who received PUVA now enrolled in the 16-center PUVA Follow-Up Study will further elucidate the poten- tial risk. In the meantime, for each patient the risk: benefit ratio of PUVA should be considered.



Table I. Cont'd

Author(s)

Johnson la (Nor- way) 1984

Kemmett et al.14 (U.K.) 1984

I Age (yri/ �9 sex/race

22 /F /W

61 /M/W

Type of melanoma

Family history of melanomal dysplastie nevus

March 1983, brown macule noted on palm of right hand 3-4 mm in diameter: intra- epidermal malignant SSM

Melanoma discov- ered April 1984; modular malignant melanoma to subcutaneous fat (level V)

NR

NR

I Type of treatment given for melanoma

Excision

Excision with wider reexcision 1 wk later

Binet et al.~5 761M/NR Malignant melanoma level II, 0.2 mm deep

NR Excision

PUVA follow-up study (U.S.A.) Case 1

Case 2

5 1 / M / W SSM

67 /F /W SSM

No

Yes

Excision with reexcision

Excision

Case 3 5 3 / M / W Not defined Yes Excision

Present case 6 1 / M / W (U.S.A.)

May 1981, noticed brown macule on right elbow: SSM level II infiltration to 0.65 ram; August 1985, brown macule on right shoulder

No May 1981, excision biopsy followed by reexcision with clear margins; August 1985, wide excision with clear margins

We thank Dr. R. W. Phillips for referring the patient described in the case report to us.

REFERENCES 1. Stem RS, Laird N, Melski J, Parrish JA, Fitzpatrick TB,

Bleieh HL, Cutaneous squamous-cell carcinoma in pa-

tients treated with PUVA. N Engl J Med 1984;310:1156- 61.

2. Parrish JA, Fitzpatrick TB, Tanenbaum L, Pathak MA. Photoehemotherapy of psoriasis with oral methoxsalen and longwave ultraviolet light. N Engl J Med 1974; 291:1207-11.

3. Ingraham DM, Bergfeld WF, Bailin PL, Steck WD, Tay- lor JS, Tomecki KJ. Long-term and short-term histo-



Results of treatment of skin cancer Skin type

NR NR

NR NR

NR NR

No recurrence II

No recurrence III

No recurrence Ill

May 1986, no evidence of recurrence

pathologic changes in the skin after PUVA therapy. Cleve Clin Q 1983;50:133-9.

4. Hrnigsmann H, Wolff K, Gschnait F, Brenner W, Jaschke E. Keratoses and nonmelanoma skin tumors in long-term photochemotherapy (PUVA). J AM ACAD DER- MATOL 1980;3:406-414.

5. Abel EA, Reid H, Wood C, Hu C-H. PUVA induced

melanocytie atypia: Is it confined to PUVA lentigines? J AM ACAD DERMATOL 1985;13:761-8.

6. Rhodes AR, Harrist TJ, Momtaz T-K. The PUVA- induced pigmented macule: a lentiginous proliferation of large, sometimes cytologically atypical, melanocytes. J AM ACAD DERMATOL 1983;9:47-58.

7. Stem RS, Parrish JA, Fitzpatrick TB. Ocular findings in patients treated with PUVA. J Invest Dermatol 1985; 85:269-73.

8. Melski JW, Tanenbaum L, Parrish JA, Fitzpatrick TB, Bleich HL, and 28 participating investigators. Oral methoxsalen photochemotherapy for the treatment of psoriasis: A cooperative clinical trial. J Invest Dermatol 1977 ;68:328-35.

9. Miettinen S. Estimability and estimation in ease-referent studies. Am J Epidemiol 1976;103:226-35.

10. Forrest JB, ForrestJH. Case report:Malignant melanoma arising during drug therapy for vitiligo. J Surg Oncol 1980;13:337-40.

11. Frenk E. Malignant melanoma in a patient with severe psoriasis treated by oral methoxsalen photochemotherapy. Dermatologica 1983;167:152-4.

12. Marx JL, Auerbach R, Possiek P, Myrow R, Gladstein AH, Kopf AW. Malignant melanoma in situ in two patients treated with psoralens and ultraviolet A. J AM ACAD DERMATOL 1983;9:904-11.

13. Johnson J. Melanoma and psoralens and ultraviolet A [Letter]. J AM ACAD DERMATOL 1984; 11:143.

14. Kemmett D, Reshad H, Baker H. Nodular malignant melanoma and multiple squamous cell carcinomas in a patient treated by photochemotherapy for psoriasis. Br Med J 1984;289:I498.

15. Binet O, Bruley C, Beltzer-Garelly E, Cesarini JP. Ma- lignant melanoma after treatment with ultraviolet A rays and psoralen. Nouv Presse Med 1985;14:1842.

16. Horm JW, Asiru AJ, Young JL, Pollack ES. SEER Pro- gram: Cancer incidence and mortality in the United States 1973-81. National Institutes of Health publication No. 85-1873. Bethesda, MD: Department of Health and Hu- man Services, 1984.

17. Henseler T, Christophers E, Hrnigsmann H, Wolff K, and nineteen other investigators. Skin tumors in the European PUVA Study. J AM ACAD DERMATOL 1987; 16:108-16.

18. Sober AJ, Mihm MC, Fitzpatrick TB, Clark WH. Ma- lignant melanoma of the skin, and benign neoplasms and hyperplasias of melanocytes in the skin. In: Fitzpatrick TB, Eisen AZ, Wolff K, Freedberg IM, Austen KF, eds. Dermatology in general medicine. 2nd ed. New York: McGraw-Hill, 1979;630.

19. Evans D, Morrow KJ. 8-Methoxypsoralen induced alterations of mammalian cells. J Invest Dermatol 1979; 72:35-41.

20, Stem RS, Fitzpatrick TB, Honigsmann H, Wolff K, Par- fish JA. Oral psoralen photoehemotherapy. In: Roenigk HH Jr, Maibaeh HI, eds. Psoriasis. New York: Marcell Dekker Inc, 1985:475-93.

21. Rhodes AR, Stem RS, Melski JW. The PUVA lentigo: An analysis of predisposing factors. J Invest Dermatol 1983;18:459-63.

22. Nakagawa H, Rhodes AR, Momtaz-TK, Fitzpatrick TB.

Gupta et al. Journal of the


Morphologie alterations of epidermal melanocytes and melanosome in PUVA lentigines. A comparative ultrastructural investigation of lentigines induced by PUVA and sunlight. J Invest Dermatol 1984;82:101-7.

23. Zelickson AS, Mottaz JH, Muller SA. Melanocyte changes following PUVA therapy. J AM ACAD DERMATOL 1979; 1:422-30.

24. Gellin GA, Kopf AW, Garfinkel L. Malignant melanoma--a controlled study of possible associated factors, Arch Dermatol 1969;99:43-8.

25. Consensus Development Panel. Precursors to malignant melanoma. National Institutes of Health Consensus De- velopment Conference Statement, Oct 24-26, 1983. J AM ACAD DZRMATOL 1984;10:683-8.

I II II I I I I

Fish oil supplementation results in decreased hypertriglyceridemia in patients with psoriasis undergoing etretinate or acitretin therapy J. M. Ashley, M.S.P.H. , R.D.,* N. J. Lowe, M.D., F.R.C.P.,** M. E. Borok, M.D.,** and R. B. Alfin-Slater, Ph.D.* Los Angeles, CA

Although retinoid derivatives are an effective treatment for severe psoriasis, they result in systemic toxicity, including hyperlipidemia. In an attempt to reverse this retinoid-related hyperlipidemia in patients with psoriasis, a prospective 4-week pilot study of fish oil supplementation was carried out in 25 patients with psoriasis vulgaris receiving etretinate (Ro-10-9359) or acitretin (Ro 10-1670). Daily fish oil supplements containing 3 gm of oJ-3 fatty acids (1.8 gm of eicosapentaenoie acid 20:5(03, and 1.2 gm of docosahexaenoic acid 22:6to3) were found to be effective in reducing hypertriglyceridemia, with a significant mean reduction from 215.6 • 92.5 to 156.9 _+ 58.5 mg/dl ( -27%) when compared with controls (203.6 + 46.9 to 204.1 • 54.3 mg/dl). High-density lipoprotein cholesterol levels increased from 41.4 _+ 10.5 to 46.1 ___ 10.8 rag/all (+ 11%), and the ratio of total cholesterol to high-density lipoprotein cholesterol decreased from 6.6 + 1.9 to 5.9 • 1.7 ( - 11%). It is concluded that fish oil supplementation may prove a valuable adjunct to ameliorate the lipid changes secondary to retinoids. (J AM ACAD DERMATOL 1988;19:76-82.)

From the Nutrition Division, University of California-Los Angeles School of Public Health,* and Dermatology Division, University of California-Los Angeles School of Medicine.**

Supported by a grant from Aida Grey, Beverly Hills, CA. Accepted for publication Feb. 8, 1988. Reprint requests to: Dr. Nicholas J. Lowe, Dermatology Division,

UCLA School of Medicine, Center for the Health Sciences, Uni- versity of California, Los Angeles, CA 90024.

The synthetic vitamin A derivatives, etretinate (Tegison) and acitretin (Soriatane) have been shown to be effective agents in the treatment of various dermatologic disorders, including severe psoriasis.~5 Etretinate is an ester that is metabol- ically hydrolized to its free acid, acitretin, which has a markedly shorter half-life. 6 However, one of

76

cutaneous melanomas in patients treated with psoralens plus ultraviolet a

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