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Calcineurin inhibitors under occlusion – I could’ve had a V8!

DII small banner By Warren R. Heymann, MD
June 6, 2017

I have used topical steroids under occlusion for as long I have been in dermatology. What a fabulous maneuver this is for difficult to treat dermatoses such as lichen simplex chronicus, recalcitrant psoriasis, or hypertrophic lichen planus, etc. I recommend Saran wrap (and tell patients that they can choose any color they want!), usually just at night, when the pruritus is worse, and they are likely not to make any noise. When I was dating a girl as a medical student, in the company of her parents, I asked out loud “What’s that crinkling noise I’m hearing every few seconds?” She told me that her father was using fluocinonide under occlusion for his psoriasis and I was hearing him step on the wrap. How embarrassed he must have been! I felt awful. I’m not opposed to occlusive therapy during the day, but I tell patients to be aware of the potential auditory component.

For whatever reason, I have never thought about using calcineurin inhibitors under occlusion, although I recommend them in sensitive that are naturally occluded (such as in cases of inverse psoriasis or inverse lichen planus). The advantages over steroids in skin folds or on the genitalia is that they are far more effective in these sites and atrophy is avoided. To my knowledge, systemic absorption to any significant degree has not been a problem for either tacrolimus or pimecrolimus when used in this manner.
Bhari and Gupta presented five men, aged 48 to 70 years old, with recalcitrant, pruritic chronic actinic dermatitis of the face and upper extremities. They state that “The patients had received oral corticosteroid (prednisolone 20–40 mg) and azathioprine 100 mg daily for a mean of 12 months, with only mild initial improvement followed by relapse. Patch and photo-patch tests were positive to parthenium acetone extracts (1:100) and (1:200) in all of them, but phototesting was not done. We advised these patients to use topical tacrolimus 0.1% ointment under occlusion using cling film once in the night. Only sunscreens and oral antihistamines were prescribed in addition to the topical treatment. Patients noticed improvement within 48 hours of starting this treatment, which was subsequently maintained for approximately 2 years in two of them, until the last follow-up visit. The effect was also maintained in the remaining three. The frequency was reduced from daily to twice and then once weekly as per the response of the patient. No adverse effect was noted in these patients.” (1)
How brilliant! That was an “I could’ve had a V8!” revelation. Why hadn’t I ever thought of that? The vital question, however, is whether occlusion allows tacrolimus to have its effect locally, or is enough absorbed to yield a systemic effect? Serum levels tacrolimus were not obtained in their study.

There is a paucity of articles addressing systemic absorption of topical calcineurin inhibitors under occlusion.

Hartmann et al treated 30 adult vitiligo patients with tacrolimus 0.1% ointment twice daily, and compared the results with those of placebo ointment. In 20 patients, defined areas on the right arm or leg were occluded overnight with 3 different dressings. After 6 months, treatment was stopped in 7 of 30 patients as they did not show any repigmentation, 5 of them had no occlusive therapy. After 12 months, 17 of 21 patients (81%) with facial involvement showed repigmentation of the face. Although no or minimal repigmentation occurred on the extremities when using tacrolimus ointment alone, 80% of the patients showed repigmentation on the arms when using additional occlusive, especially hydrocolloid dressings. Hands, feet and lower legs were unresponsive. The best results were obtained in patients with long-standing vitiligo. Only minimal side effects were noted. There was no significant elevation in tacrolimus blood levels, taking into account that occlusion was performed only on limited parts of the body. The authors concluded that tacrolimus 0.1% ointment is an effective and safe treatment option for adult patients with vitiligo. Beyond the face and neck areas, repigmentation could be achieved only by additional occlusion. (2)
Another study by Hartmann et al (with the same coauthors) of a 15 year-old girl with large pretibial lesions of progressive vitiligo was treated twice daily over six months with 0.1% tacrolimus ointment on the right and 1% pimecrolimus cream on the left side, without effect. Additional overnight occlusion with polyurethane and hydrocolloid foils during the following 18 months led to substantial repigmentation on both sides (tacrolimus-treated side, 88% repigmented area; pimecrolimus-treated side, 73%). Tacrolimus serum levels measured at four different time points did not exceed 1.8 ng/ml. This direct comparison of topical tacrolimus and pimecrolimus in vitiligo demonstrated that considerable improvement could be induced with both agents only by additional long-term occlusion. Tacrolimus was somewhat more effective than pimecrolimus (3)

These are not large, prospective, blinded studies. I still question how much absorption exists, especially over large areas. This would certainly be more worrisome in the context of other disorders such as pyoderma gangrenosum where occlusive tacrolimus has been utilized under occlusion, but without the measurement of systemic levels. (4)

Nevertheless, I use systemic immunomodulators for patients with severe chronic actinic dermatitis and patients with vitiligo are inquiring about the use of JAK inhibitors. If looked at from that vantage point, why not give calcineurin inhibitors under occlusion a try?

1. Bhari N, Gupta S. Tacrolimus 0.1% ointment applied under occlusion using cling film clears chronic actinic dermatitis resistant to systemic treatment. Int J Dermatol 2017; 56; e139-41.
2. Hartmann A, et al. Occlusive treatment enhances efficacy of tacrolimus 0.1% ointment in adult patients with vitiligo: Results of a placebo-controlled 12 month prospective study. Acta Derm Venereol 2088; 88: 474-9.
3. Hartmann A, et al. Repigmentation of pretibial vitiligo with calcineurin inhibitors under occlusion. J Dtsch Dermatol Ges 2008; 6: 383-5.
4. Kontos A, et al. An open-label study of topical tacrolimus ointment 0.1% under occlusion for the treatment of pyoderma gangrenosum. J Am Acad Dermatol 2005; 52S; 115.

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