Oral methoxsalen photochemotherapy of extensive pityriasis alba

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Oral methoxsalen photochemotherapy of extensive pityriasis alba Preliminary report Shukrallah Zaynoun, M.D., Lina Abi Ali Jaber, B.Sc., and Amal K. Kurban, M.D.

Beirut, Lebanon Six patients with extensive pityriasis alba were treated with oral methoxsalen, followed by exposure to midday summer sun or exposure to long-wave ultraviolet radiation in a psoralens plus ultraviolet A (PUVA) cabinet. Complete clearing or marked improvement was obtained in five patients in less than 4 weeks of treatment. The patient with the most extensive skin involvement and the longest duration of the disease achieved a marked degree of improvement after 15 weeks of therapy. A long-term follow-up is still required to define the maintenance treatment and its efficacy. (J AM ACADDERMATOL15:61-65, 1986.)

Pityriasis alba is a relatively common skin disorder, usually seen in children. The lesions are frequently present on the face, arms, and shoulders. Initially the typical lesion consists of an itregular, round or oval, pink patch, sometimes with an elevated, slightly erythematous border, varying in size from a few millimeters to a few centimeters. After some weeks the erythema usually fades, leaving a whitish macule covered by fine scales. Not infrequently, however, we have encountered patients with extensive symmetric involvemerit of the skin, frequently of the lower half of the trunk, consisting of smooth, nonscaly, circumscribed, whitish macules. The lesions were asymptomatic and were not preceded by erythema or other signs of inflammation. There was no response to emollients or topical steroids. In all these From the Department of Dermatology, American University of Beirut-Medical Center. Supported by the Lebanese Council for Scientific Research, Grant No. 38-5786, and the University Research Board, American University of Beirut, Grant No. 18-5129. Accepted for publication March 20, 1986. Reprint requests to: Dr. Shukrallah Zaynoun, Department of Dermatology, American University of Beirut-Medical Center, 850 Third Ave., New York, NY 10022.

Table I. Clinical data Duration

of

Case Age

No.

(yr)

Sex

1

27

Female

6 yr

2

23

Female

6 yr

3 4

22 25

Female Female

4 yr 3 yr

5 6

27 29

Female Female

2 mo 12 yr

condition

Distribution of lesions

Lower half of trunk Lower half of trunk; minimal lesions on arms and cheeks Lower half of trunk Trunk; minimal lesions on arms Trunk Extensive involvement of neck, trunk, and arms; minimal lesions on face

patients there was no evidence suggesting any specific disease entity such as pityriasis versicolor, postinflammatory hypopigmentation, particularly following the clearing of papulosquamous disorders, secondary syphilis, drug eruptions, and papular urticaria that might have resulted in this mor61

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T a b l e II. Treatment and results

Case No.

1

2

3

4

5

Source of irradiation, frequency, and number of exposures and dose of UVA

Degree of response

Maintenance treatment

Follow-up

None No recurrence 1 mo after Sun exposure, three times/wk Cleared completely therapy was stopped for 2 wk; then daily for 1 by patient wk; 13 exposures, 60-90 min each Cleared completely Sun exposure, daily treatOne treatment/wk No recurrence 1 mo after treatment was disconment; 9 exposures, 30-45 for 1 mo tinued by patient min each Lost to follow-up Sun exposure, three times/wk Marked improvement None for 2 wk; 6 exposures, 15-30 min each Lost to follow-up No improvement Psoralite, three times/wk for None with Psoralite; 3 wk, 9 exposures, 40 marked improvejoules; then sun 3 times/ ment with sun wk; 4 exposures, 90 rain each Complete clearing Remained c/ear 7 mo One treatment Psoralite, three times/wk; 7 after 5 sessions every 2 wk for after treatment was exposures, 39 joules 1 mo discontinued Relapsed while on mainPsoralite, three times/wk; 48 Marked improvement One treatment, after 45 sessions 6.5 joules/wk tenance treatment exposures, 288 joules for 5 wk

phologic pattern. Furthermore, the clinical picture contrasted with the widespread lesions of pityriasis alba seen in atopic dermatitis. In the latter there is usually a personal and/or family history of atopy and atopic dermatitis and generalized dryness of the skin. In addition, the lesions associated with atopic dermatitis are frequently scaly, are not smooth to touch, and may be erythematous and pruritic. Furthermore, they usually respond to topical remedies, including emollients and corticosteroids. The patients with extensive involvement of unknown etiology and not related to atopy or atopic dermatitis may represent either a variant of pityriasis alba or perhaps a new entity. In this study we refer to this condition as extensive pityriasis alba. Patients with extensive pityriasis alba are not uncommonly seen in Lebanon and are probably more frequently encountered than patients having extensive vitiligo. The condition presents a cosmetic problem especially during the swimming seasons. Although some patients improve or even clear after repeated sun exposure, the majority be-

come much worse because of hyperpigmentation of the surrounding skin and lack of response of the hypopigmented patches. In a previous study on extensive pityriasis alba,~ it was demonstrated that the hypopigmentation results primarily from reduction in the number of active melanocytes and a decrease in the number and size of melanosomes in the affected skin. Since oral psoralen photochemotherapy has been shown to stimulate melanocyte proliferation and activity and has been used successfully in the treatment of vitiligo, 2 we planned to assess the efficacy of this therapeutic modality in patients with extensive pityriasis alba. PATIENTS AND METHODS Clinical data. Six patients with extensive pityriasis alba were studied. All were adult women 22 to 29 years of age (Table I). All had skin type IV. The duration of the condition ranged from 2 months to 12 years. The lesions were asymptomatic; they were persistent throughout the year but more apparent during spring and summer. There was no personal or family history of atopy and no family history of pityriasis alba except

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Methoxsalen photochemotherapy of pityriasis alba 63

Fig. 1. A, Patient 1 with a 6-year history of extensive pityriasis alba. B, Same patient, showing complete clearing of skin lesions after 3 weeks of treatment with 40 mg of methoxsalen and sun exposure. that two of the patients under study were siblings (patients 5 and 6). There was no history of a preceding inflammatory skin disease. The skin findings consisted of whitish macules that were distributed symmetrically over the lower half of the trunk in three patients, the whole trunk in two patients, and the trunk, neck, and arms in one patient. Minimal involvement of the face was noted in two patients. The lesions were smooth to touch; there was no evidence of scaling or erythema, and the hair within the lesions appeared normal in color. The condition was not responsive to emollients and/or topical corticosteroids. Potassium hydroxide

preparations from scrapings failed to reveal any fungal elements. Photoehemotherapy. Treatment was usually given three times per week. Two hours prior to exposure to long-wave ultraviolet radiation (UVA) or sun, the patients ingested approximately 0.6 mg/kg of methoxsalen (8-MOP). Three patients had midday sun exposure during the summer months throughout the course of therapy (patients, 1, 2, and 3). Treatments were given three times per week in two patients and daily in the third. The other three patients were given UVA irradiation in a PUVA cabinet (Psoralite, Elder Pharmaceuticals,

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Fig. 2. A, Patient 4, before treatment. B, Same patient showing marked improvement after photochemotherapy. Bryan, OH). The initial dose was 2 joules/cm2, which was gradually increased according to the response and tolerance of the patients. The highest individual dose was 6,5 joules/cm2. The number of treatments and cumulative UVA doses are shown in Table II. Patient 4 received UVA irradiation in the PUVA cabinet for 2 weeks and showed no improvement. She was then shifted to sun exposure. RESULTS

Three patients achieved complete clearing of lesions, and the other three showed marked improvement (Table II). Patients 1 and 2 cleared

after nine to thirteen exposures of 30 to 90 minutes of midday summer sun (Fig. 1). Patient 1 did not receive any maintenance therapy and did not show any signs of a relapse when last seen 1 month after treatment was discontinued. Also, Patient 2 showed no sign of relapse while on a maintenance weekly exposure for 1 month. However, she was lost to follow-up. Patient 3 showed marked improvement after six sun exposures of 15 to 30 minutes each. Patient 4 failed to respond to six treatments with PUVA; however, she showed marked improvement after four exposures to 90 minutes of sunshine, with-

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Methoxsalen photochemotherapy of pityriasis alba 65

out any change in the dose of 8-MOP (Fig. 2). Patient 5, who had the condition for only 2 months, cleared after five treatments with PUVA. She was then given one treatment every 2 weeks for 1 month. When last seen 7 months later she was still free from lesions. Patient 6, who had the most extensive skin involvement and the longest duration of the disease, required the greatest number of PUVA sessions (48 treatments, 288 joules). She started to show signs of a relapse while on a weekly maintenance dose Of 6.5 joules. This was stopped 4 weeks later. All lesions recurred 1 month after maintenance therapy was discontinued. DISCUSSION The results of this preliminary work demonstrate the effectiveness of oral photochemotherapy in extensive pityriasis alba with the use of 8-MOP. The response was relatively prompt compared to that obtained in the treatment of vitiligo. Five patients achieved complete clearing or marked improvement in less than 1 month of treatment, irrespective of the source of irradiation used. The lesions on the abdomen and sides of the trunk tended to respond more quickly than those on the back. The relatively slow response noted in the sixth patient may have resulted from the long duration and extent of the disease. The possibility that the response may have resulted from natural remission seems unlikely because of the persistence of the condition almost unchanged for 3 to 12 years in five of the patients under study. It should be remembered, however, that these patients had skin type IV and therefore no extrapolation as to a similar therapeutic effect can be made for patients with other skin types. Unfortunately, an adequate follow-up was generally not possible because of the unpredictable demographic changes of the war in Lebanon. Therefore, the frequency and duration of maintenance therapy were not defined properly. It is reassuring, however, that two of the patients remained free from lesions 1 and 7 months, respectively, after photochemotherapy was discontinued.

Also, a third patient remained clear while on a maintenance treatment for 1 month. None of the patients had any significant side effects from the treatment and no appreciable erythema was observed during therapy. All patients developed a uniform, cosmetically acceptable hyperpigmentation of the skin. It is of note that all six patients included in this study were women. Similarly, seven of the nine patients with extensive pityriasis alba who were studied previously ~ were female. This may represent a true preponderance of idiopathic extensive pityriasis alba in women. However, we cannot exclude the possibility that women are more motivated to seek treatment for a purely cosmetic dermatologic condition than are men. The mechanism of action of photochemotherapy in extensive pityriasis alba is not clear. Oral psoralens and UVA exposure have been shown to induce pigmentation of the skin by increasing the number and activity of functional melanocytes, the number of melanosomes, and the transfer of melanosomes to keratinocytes. 3 It would, therefore, be important in future work to evaluate all these melanocyte parameters before, during, and after psoralen photochemotherapy with the use of histologic, histochemical, and ultrastructural studies. An assessment of the value of other psoralen compounds, such as trioxsalen, in oral and topical photochemotherapy of extensive pityriasis alba is also indicated. Also, smaller doses of psoralens and UVA should be assessed in order to minimize the risks of photochemotherapy. REFERENCES 1. Zaynoun ST, Aftimos BG, Tenekjian KK, et al: Extensive pityriasis alba: A histological, histochemical and ultrastructural study. Br J Dermatol 108:83-90, 1983. 2. Parrish JA, Fitzpatrick TB, Shea C, Pathak MA: Photochemotherapy of vitiligo. Use of orally administered psoralens and a high-intensity long-wave Ultraviolet light system. Arch Dermatol 112:1531-1534, 1976. 3. Pathak MA, Kramer DM, Fitzpatrick TB: Photobiology and photochemistry of furocoumarins (psoralens), in Pathak MA, Harber LC, Seiji M, et al, edifors: Sunlight and man, normal and abnormal photobiologic responses. Tokyo, 1974, University of Tokyo Press, pp. 335-368.