Abnormalities oj pigmentation following UVB and topical therapy Ab,wrmalities oj pigmentation jollowing UVB exposure and incorrect appllcation oj calcipotriol ointment and tazarotene geljor psoriasis G. Stinco, A. Frattasio, P. Mattighello, V. De Francesco and P. Patrone S UMMARY We present two cases where an incorrect application of the topical therapy in association with UVB phototherapy caused hyper- or hypopigmented skin lesions. CASE 1. A 48-year-old man with plaque psoriasis treated with calcipotriol ointment plus UVB phototherapy. Although correctly instructed, on one occasion he applied the calcipotriol ointment a few minutes before the UVB exposure. Some hours later he presented numerous irregular hypopigmented areas around the psoriatic lesions. The calcipotriol therapy plus UVB phototherapy was continued and the hypopigmentation areas gradually cleared in about a month. CASE 2. A 48-year-old man with plaque psoriasis treated with tazarotene 0.1 % gel plus UVB phototherapy. Although correctly instructed, he applied tazarotene gel one hour before the UVB exposure. The results was the sudden appearance of numerous dark-brown hyperpigmentation in the form of asymptomatic round or oval patches on the site of psoriatic lesions involving his trunk and limbs. The treatment was discontinued and the hyperpigmentated patches lasted for a further 6 months. Background Calcipotriol is a new vitamin D analogue w hile tazarotene is the first of a new generation of acetylenic retinoids, which have praven to be efficacious in the treatment of mild to moderate plaque psoriasis (1 , 2). These topical preparations are cosmetically acceptable, generally well tolerated and are minimally absorbed systemically; the adverse events are limited to local irritation (2, 3). Recent studies indicate that calcipotriol can be combined with UV therapy (4, 5). In preclinical toxicity studies, topically applied, tazarotene was neither teratogenic nor carcinogenic and was not sensitizing, phototoxic, or photosensitizing (6, 7). We report two cases where an incorrect application of calcipotriol or tazarotene gel in association with TNB photothe rapy caused resp ec tively hypo- o r hyperpigmented skin lesions. Case report CASE 1: A 48-year-old man with plaque psoriasis was treated w ith calcipotriol ointment plus TNB photo- Case re p ort K E Y WORDS psoriasis, calcipotriol, tazarotene, side effects, hypo- pigmentation, hyper- pigmentation 122 acta dermatovenerologica A.P.A. Vol 8, 99, No 3 Case report Fig. 1 . Numerous irregular hypopigmented areas appeared after UVB exposure in correspondence to the psoriatic lesions presenting a form which matched the site of application of calcipotriol ointment. therapy. Although we had instructed the patient to apply a thin film of the medication to ali psoriatic lesions (excluding those on the face , flexor, and intertriginous areas) once daily, in the evening, on one occasion he applied the calcipotriol ointment a few minutes before the lNB exposure . Some hours after the exposure he presented numerous irregular hypopigmented areas around the psoriatic lesions (Fig. 1). The pacient enjoyed a good health and had not taken any drug in the last months. Routine laborato1y parameters were normal. He refused a biopsy needed for a histopathological examination. The calcipotriol therapy plus lNB photo- therapy was continued and the hypopigmentation areas gradually cleared in about a month. CASE 2: A 48-year-old man with plaque psoriasis was treated with tazarotene 0.1 % gel plus lNB photo- therapy. Although the pacient was instructed to apply a thin film of the medication to ali psoriatic lesions (excluding those on the face, flexor, and intertriginous areas) once daily in the evening, he applied tazarotene gel in the morning, one hour before the lNB exposure. The result was the sudden appearance of numerous dark-brown hyperpigmentations in the form of asymp- tomaric round or oval patches ar rhe site of the psoriatic lesions on his trunk and limbs (Fig. 2). The pacient reported to have always been in good health and had not taken any drug during the last months. Routine laboratory parameters were normal. The pacient refused Abnonnalities of pigmentation following UVB and topical therapy to give his consent to undergo a biopsy for a histopatho- logical examination. The treatment was cliscontinued but the hyperpigmentatecl patches lastecl for further 6 months. Discussion The incorrect use of topical therapy before lNB ex- posure can cause different side effects. These 2 cases seem to suggest that the ointment containing calcipotriol inhibits lNB penetration, while the gel containing taza- rotene appears to contain a phototoxic factor. In the first case, we observed hypopigmented pat- ches on the site of application of calcipotriol ointment. Although the pacient continued phototherapy treatment, the lesions remained visible. This shows that the lesions were not only determined by the barrier effect of the Fig. 2. Numerous dark-brown hyperpigmented patches appeared on the sites of psoriatic lesions following application of tazarotene gel and UVB exposure. acta dermatovenerologica A.P.A. Vol 8, 99, No 3 ----- - ------ ---------------- ---- 123 Abnormalities of pigmentation following UVB and /opica/ rherapy calcipotriol ointment, but that the active principle or the vehicle acted on the melanin pigmentary system. The absence of a histopathological and of histochemical examinations did not allow us to establish the site of the damage. Pigmenta1y disorders have already been reported on lesional skin after vitamin D3 analogues ancl UV exposure . Hype rpigmentation bas been observecl as side effect after combined treatment w ith calcipotriol and heliotherapy (8) or bath-PUVA (9). On the contrary, hypopigmentation h as never been describecl. In view of a possible importance of this observation, further studies on a larger number of patients are suggested. In the second case, the hyperpigmented patches appeared after UVB exposure on the site of application of tazarotene gel. So far we have not noticed similar hyperpigmentations in other patients who have under- gone the same treatment but kept to the instructions to apply the tazarotene gel in the evening , at least 12 hours prior to UV exposure. Consequently, in the absence of other etiologic factors , it may be concluded that the topical application of tazarotene a short tirne before phototherapy is resp onsible for the appearance of hyperpigmentation. AUTHORS' ADDRESSES 1. Murdoch D, Clissold SP. Calcipotriol: a review of its pharmacological properties and therapeutic use in psoriasis vulgaris.Drugs 1992; 43: 415-29. 2. Weinstein GD. Tazarotene gel: efficacy and safety in plaque psoriasis. J Am Acad Dermatol 1997; 37: S33-38. 3. Kragballe K, Fogh K, Sogaard H. Long-term efficacy and tolerability of to pica! calcipotriol in psoriasis: results of an open study. Acta Derm Venereol (Stockh) 1995; 71: S 475-8. 4. Kokelj F, Lavaroni G, Guadagnini A. UVB versus UVB plus calcipotriol (MC 903) therapy for psoriasis vulgaris. Acta Derm Venereol (Stockh) 1995; 75: 386-7. 5. Koo J. Calcipotriol/calcipotriene (Dovonex/Daivonex) in combination with phototherapy: a review. J Am Acad Dermatol 1997; 37: S59-61. 6. Marks R. Clinical safety of tazarotene in the treatment of plaque psoriasis. J Am Acad Dermatol 1997; 37: S25-32. 7. Chandraratna RA. Tazarotene: the first receptor-selective topical retinoid for the treatment of psoriasis. J Am Acad Dermatol 1997; 37: S12-7. 8. Kokelj F, Lavaroni G, Perkan V, et al. I-Iyperpigmentation due to calcipotriol (MC 903) plus heliotherapy in psoriatic patients. Acta Derm Venereol (Stockh) 1995; 75: 307-9. 9. Glaser R, RowertJ, MrO\vietz U. Hyperpigmentation due to topical calcipotriol and photochemotherapy in two psoriatic patients. Br J Dermatol, 1998; 139: 148-51. Giuseppe Stinco, MD, dermatologist, Institute ojDermatology, D.PM.S.C., University ojUdine, GenwnaHospital, 33013 Gemona delFriuli (Udine), Italy Alfonsina Frattasio, MD, dermatologis t, same address Paolo Mattighello, MD, dennatologist, same address Vincenzo De Francesco, MD, dennatologist, same address Pasquale Patrone, MD, proj'essor oj dermatology, Head oj Institute, same address Case re po rt 124 - - - ---- - - - - --- --~ acta dermatovenerologica A.P.A. Vol 8, 99, No 3