Calcitriol

Abstract

We describe 3 cases of psoriatic patients who developed a severe eczematous eruption after the use of calcipotriol ointment. For all of them, the dermatitis recovered after the suspension of the calcipotriol ointment and topical application of corticosteroids. We performed patch tests with the standard series of SIDAPA (Italian Society of Environmental, Occupational and Allergological Dermatology), with an integrative series of vehicles and preservatives, with the commercial ointment containing calcipotriol, with its excipients and, finally, with a series of diluted calcipotriol in isopropanol and petrolatum. They all revealed a strong allergic reaction to calcipotriol and also to its dilution in isopropanol (for all patients) and in petrolatum (only one patient). It is interesting to underline that the reactions always occurred on the legs, even if the patients had applied the ointment elsewhere. We can hypothesize that the venom stasis dermatitis of the legs, associated with xerosis, may have favored the penetration of the drug through the skin, increasing the risk of allergic contact sensitization. Finally, cross-reactivity to other vitamin [D.sub.3] analogue, tacalcitol, and calcitriol was excluded.

Introduction

Calcipotriol is a vitamin D analogue with antiproliferative and anti-inflammatory effects. It is used with success for the treatment of mild-to-moderate plaques psoriasis. (1,2) A common side effect of calcipotriol is irritant contact dermatitis, while allergic contact dermatitis is rarely reported. (3-5) We describe 3 patients who developed an eczematous eruption after the use of a calcipotriol ointment.

Case Report 1

A 75-year-old man with positive anamnesis for venous varices of the limbs and a 40-year history of psoriasis vulgaris, affecting trunk, limbs, and nails alternatively treated with hydrocortisone, bethametasone, mometasone, calcipotriol, and cycles of psoralen photochemotherapy. The patient presented with an eczematous eruption on the limbs, trunk, and buttocks for 2 months, which developed after the use of calcipotriol ointment (Daivonex[R], Formenti, Milan) twice a day.

Clinical examination showed an erythemato-vesicular eruption of the limbs and buttocks aside from common psoriatic lesions involving the trunk, buttocks, limbs, elbows, and knees. The dermatitis healed 2 weeks after the suspension of the calcipotriol ointment and following the treatment with topical corticosteroids.

Case Report 2

A 70-year-old woman with a history of follicular lichen planus, allergic contact dermatitis to nickel sulphate, and psoriasis localized at the elbows, knees, and legs was admitted in November 2004 for several eczematous lesions of the limbs, which had appeared 1 month before. Her medical history included arterial hypertension, asthmatic bronchitis, and stasis dermatitis. Previous antipsoriatic treatments consisted of various topical drugs, including salicylic acid, corticosteroids, and dithranol. In August 2004, she started to use ointments containing calcipotriol and bethamethasone (Dovobet[R], Formenti, Milan) and then only calcipotriol (Daivonex[R]). One month after the application of the calcipotriol ointment twice a day, she developed a strong eczematous reaction particularly on the legs. The use of the ointment was stopped and the patient was successfully treated with topical corticosteroid.

Case Report 3

A 72-year-old man with a past history of cerebral ischemic stroke and affected by stasis dermatitis of the legs and mild chronic plaques-type psoriasis of the scalp, elbows, and knees developed a strong eczematous reaction of the limbs after 2 months of twice a day use of calcipotriol ointment (Daivonex[R]). Clinical examination revealed large erythemato-exudative lesions of the legs and psoriatic plaques involving the scalp and the elbows. The dermatitis resolved after suspension of the calcipotriol ointment and topical application of corticosteroids.

Material and Methods

The patients in all 3 case reports were patch tested with the SIDAPA (Italian Society of Environmental, Occupational and Allergological Dermatology) standard series, with an integrative series of vehicles and preservatives, the commercial ointment containing calcipotriol, its excipients and with a series dilution of calcipotriol in isopropanol and petrolatum and with other vitamin D derivatives in petrolatum (calcitriol and tacalcitrol). Patch tests were performed using Al-tests[R] (Imeco AB, Sodertalje, Sweden). Readings were made after 2, 4, and 7 days. The tests were performed during a non-dermatitis phase. Reactions were read and interpreted according to the International Contact Dermatitis Research Group Guidelines. Patch tests with the calcipotriol ointment were also performed in 10 healthy volunteers and in 5 psoriatic patients without eczematous dermatitis.

Results

Patch test results are summarized in Table 1. All patients showed positive reactions to the marketed calcipotriol ointment, 2 were positive to a dilution series of calcipotriol in isopropanol and only one was also positive to a dilution series of calcipotriol in petrolatum. None of the patients showed a positive reaction to other constituents of calcipotriol ointment or other vitamin D derivatives (calcitriol and tacalcitol). Patch tests with the calcipotriol ointment were negative in all 10 healthy volunteers and in 5 psoriatic patients.

Discussion

Calcipotriol is a topical vitamin [D.sub.3] analogue regarded by many to be the first-line treatment for mild-to-moderate plaque psoriasis. (1,2) Its use is becoming increasingly popular for its efficacy and aesthetically acceptability. However, the occurrence of lesional and perilesional irritation may preclude its use on facial lesions and on the flexures. Allergic contact dermatitis to calcipotriol seems to be rare, but probably underestimated because dermatologists rarely perform patch tests with this drug due to difficulties distinguishing allergic from irritant reactions. (3-5) In this report, we describe 3 cases of allergic contact dermatitis to calcipotriol ointment. It is interesting to underline that the reactions occurred in all cases on the legs of old patients, even if the patients had applied the ointment elsewhere. We can hypothesize that calcipotriol may induce cutaneous lesions especially when applied on compromised skin. Venom stasis dermatitis of the legs, associated with xerosis which is very common in elderly patients, may have favored the penetration of the drug through the skin, increasing the risk of allergic contact sensitization. The results of patch tests showed that all patients were positive to calcipotriol ointment as it is; one patient reacted to serial dilutions of calcipotriol both in isopropanol and petrolatum, and the other 2 patients only to serial dilutions of calcipotriol in isopropanol. The correct concentration of calcipotriol for patch testing is not well established. (3) We think that 10 [micro]g/ml of calcipotriol in isopropanol might be a suitable concentration for patch testing because at those levels the highest number of allergic results can be observed (4,6-10) with a low risk of irritative reactions. (4)

Cross-reactivity to other vitamin [D.sub.3] analogue, tacalcitol, and calcitriol was excluded, although they have a chemical structure similar to calcipotriol. That is important from a clinical point of view because vitamin [D.sub.3] analogues are widely used for the treatment of psoriasis. It confirms that very small variations in the chemical structure can modify the reactivity to molecules.

Finally, calcipotriol contact dermatitis, even if rare, should be suspected if a severe eruption develops especially in areas other than the face or skin folds.

References

1. Queille-Roussel C, Duteil L, Parneix-Spake A, Arsonnaud S, Rizova E. The safety of calcitriol 3 microg/g ointment. Evaluation of cutaneous contact sensitization, cumulative irritancy, photoallergic contact sensitization and phototoxicity. Eur J Dermatol. 2001;11:219-224.

2. Ortonne JP, Humbert P, Nicolas JF, et al. Intra-individual comparison of the cutaneous safety and efficacy of calcitriol 3 microg g (-1) ointment and calcipotriol 50 microg g (-1) ointment on chronic plaque psoriasis localized in facial, hairline, retroauricular or flexural areas. Br J Dermatol. 2003;148:326-333.

3. Krayenbuhl BH, Elsner P. Allergic and irritant contact dermatitis to calcipotriol. Am J Contact Dermat. 1999;10:78-80.

4. De Groot AC, Contact allergy to calcipotriol. Contact Dermatitis. 1994;30:242-243.

5. Molin L. Contact dermatitis after calcipotriol and patch test evaluation. Acta Derm Venereol. 1996;76:163-164.

6. Steinkjer B. Contact dermatitis from calcipotriol. Contact Dermatitis. 1994;31:122.

7. Garcia-Bravo B. Camacho F. Two cases of contact dermatitis caused by calcipotriol cream. Am J Contact Dermat. 1996;7:118-119.

8. Frosch PJ, Rustemeyer T. Contact allergy to calcipotriol does exist. Report of an unequivocal case and review of the literature. Contact Dermatitis. 1999;40:66-71.

9. Park YK, Lee JH, Chung WG. Allergic contact dermatitis from calcipotriol. Acta Derm Venereol. 2002;82(1):71-2.

10. Giordano-Labadie F, Laplanche G, Bazex J. [Contact eczema caused by calcipotriol]. Ann Dermatol Venereol. 1996;123:196-197.

Address for Correspondence

Prof. Caterina Foti MD

Department of Internal Medicine, Immunology and Infectious Diseases Unit of Dermatology

University of Bari

Policlinico, Piazza Giulio Cesare, 11

1-70124 Bari, Italy

Phone: +39 080 5478996

Fax: +39 080 5478954

e-mail: c.foti@dermatologia.uniba.it

Foti Caterina MD, Carnimeo Luigi MD, Bonamonte Domenico MD, Conserva Anna MD, Casulli Claudia MD, Angelini Gianni MD

Department of Internal Medicine, Immunology and Infectious Diseases, Unit of Dermatology, University of Bari, Bari, Italy

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