Calcipotriene/Betamethasone Dipropionate Foam as a Potential Safe and Effective Treatment of Nail Psoriasis

Abstract Background: Nail psoriasis is a common condition that affects quality of life in individuals with psoriasis and psoriatic arthritis. Topical treatments have been shown to be effective in treating nail bed disease but not as effective in treating nail matrix diseases, which often requires intralesional corticosteroids. Objectives: The objective of this open-label study was to evaluate the efficacy of combination calcipotriol/betamethasone dipropionate foam as a treatment for nail psoriasis including nail matrix disease. Method: We report three patients with moderate to severe nail psoriasis with involvement of all ten fingernails who applied study foam nightly for 6 months. Nails were assessed using the NAPSI score evaluating both nail bed and nail matrix disease. Results: NAPSI score improved including nail matrix disease in the majority of nails. No skin irritation or unexpected adverse events occurred. Conclusions: We conclude this foam combination product could be an effective and safe treatment for fingernail psoriasis and may provide better nail matrix penetration as evidenced by improvement in nail matrix score. Further studies are needed for additional evaluation.


Introduction
Nail psoriasis occurs in about 80-90% of psoriatic patients [1].It is associated with worse skin disease and development of psoriatic arthritis.Nail psoriasis also increases disease burden and negatively impacts quality of life [2].While more research is still needed, a group consensus in 2019 concluded that few nail disease (less than or equal to three-nail involvement) with nail bed involvement could be treated with topical medications, while nail matrix involvement may require intralesional corticosteroids or a systemic agent.If more nails are involved, clinician's discretion is recommended in selecting topical versus systemic treatment [3].
In a study by Tosti et al. [4], calcipotriol was as effective as a corticosteroid preparation at reducing subungual hyperkeratosis.In a separate study by Kole et al. [5], it was demonstrated that calcitriol ointment was as effective as betamethasone dipropionate ointment for the treatment of nail thickness in nail psoriasis.Furthermore, in a study by Rigopoulos et al. [6], the fixed combination formulation of calcipotriol/betamethasone dipropionate ointment was effective in the treatment of nail psoriasis , and Lind et al. [7] demonstrated that the fixed combination calcipotriene/betamethasone dipropionate foam had greater skin penetration than the ointment formulation .Two studies regarding calcipotriol/betamethasone dipropionate foam have shown that it can be effective in treating nail psoriasis [8,9].As such we proposed that the combination product of vitamin D and topical steroids in the foam formulation may penetrate the nail matrix and be an effective and safe option in the topical treatment of nail psoriasis including matrix disease without the need for intraslesional corticosteroids or systemic medications.

Materials and Methods
This was an open-label study that included three patients with moderate to severe nail psoriasis involving all ten fingernails.Inclusion criteria required previous diagnosis of skin psoriasis by a board-certified dermatologist and moderate to severe psoriasis of the fingernails.Fingernail psoriasis was confirmed by classic signs such as irregular pitting, onycholysis with red border, and oil drop dyschromia.Toenail disease was excluded.Patients with other causes of nail dystrophy such as onychomycosis or lichen planus were excluded.Onychomycosis was ruled out by absence of subungual debris or negative KOH microscopy if subungual debris were present.Lack of history of lichen planus and classic signs of lichen planus excluded lichen planus.One subject was on a stable dose of apremilast for at least 6 months and continued on this dose throughout the study.The other two subjects were not on systemic therapy for psoriasis.Eligible subjects were provided with study foam once daily .The patients applied one pea-sized amount of foam in a thin layer on the affected nails at night, immediately before bed and were asked to not wash their hands before morning.Total nail bed plus nail matrix score (NAPSI score) of affected nails was measured at each visit and nail photography was performed at each visit.

Results
A total of 3 patients and thirty fingernails were analyzed monthly during 6 months of nightly application of the foam.Eighteen out of thirty nails (60%) showed improvement in total NAPSI score (Fig. 1a, b).Sixteen out of thirty nails (53%) had improvement of nail matrix score (Fig. 2a, b).Three out of thirty nails (10%) had worsening of the total NAPSI score.The remaining of the nails had no change in total NAPSI score.No skin irritation occurred.Two out of 3 patients reported improvement in nail pain, appearance, and overall quality of life.No other reported adverse events were related to the study drug, and no serious adverse events occurred.

Discussion
Gregorio et al. [8] posited that cal/BD foam formulation would be safe and effective in treating nail psoriasis because of its antiproliferataive, anti-inflammatory, and keratinocyte differentiation properties.In accordance with our initial proposal that combination vitamin D analogs and topical steroids in foam formulation can improve nail psoriasis including matrix disease, combination calcipotriene/betamethasone dipropionate foam is a promising treatment for nail psoriasis according to reduction in total NAPSI score with no observed adverse effects such as skin irritation or systemic side effects.The fact that nail matrix score showed improvement implies that foam formulations of steroid and vitamin D analogs not only penetrate the skin better than other vehicles as other authors have written [7] but they also penetrate the nail matrix.The lack of improvement of some nails is a testament to the difficulty clearing nail psoriasis.Of interest, one study participant who was on a stable dose of apremilast prior to participation in the study, during the study and after the study ended presented for an unrelated problem 6 months after completing the study, and the nails were noted to be much worse after discontinuation of the foam while still taking apremilast.Further studies on a larger sample size will be needed to assess its effectiveness on individual components of nail psoriasis such as nail bed, nail matrix, and nail thickness.Also, we believe that the evidence of foam penetrating the nail matrix opens possibility that calcipotriene/betamethasone dipropionate foam could treat other types of nail disorders.

Statement of Ethics
This study protocol was reviewed and approved by the University of Alabama Institutional Review Board, approval number IRB-200002797-004.Written informed consent was obtained from participants prior to any study procedures.

Fig. 1 .Fig. 2 .
Fig. 1. a Significant onycholysis in a patient's left third digit at screening visit.b Improvement in onycholysis after 6 months of daily application of Enstilar foam.