Topically applied low-dose calcitriol ameliorates atopic eyelid dermatitis.

Introduction

A negative correlation between vitamin D serum levels and disease severity is increasingly documented in patients with atopic dermatitis (AD), although some contradictory results are reported. In spite of some evidence of beneficial effects of oral vitamin D supplementation in the treatment of AD, no consensus exists on its routine use in this patient group.1, 2 Although topical application of the vitamin D analogue, calcitriol, at a concentration of 3 μg/g, and its noncalcemic synthetic counterpart, calcipotriol, in an equivalent therapeutic dose of 50 μg/g (= 0.005%), is a safe and effective treatment option for psoriasis, clinical data on this type of treatment in patients with AD are generally lacking.

Case report

The subject was one of the authors (ST), a 36-year-old man who presented with AD confined to the upper and mainly lower eyelids (Fig 1, A). AD was diagnosed according to the criteria of Hanifin and Rajka. The patient had chronically relapsing periorbital dermatitis with pruritus and typical morphology (ie, erythema, fissures, scaling, and lichenification), pronounced itch when sweating, xerosis, seasonal allergic rhinitis with recurrent conjunctivitis, and a family history of atopy. The skin symptoms had lasted over a decade with spontaneous remissions, mainly during summer, and flare-ups during winter seasons. The patient did not report on the use of cosmetics, eye care products, or eye medications suggestive of contact dermatitis. The patient had an insufficient vitamin D (25[OH]D) serum level (22.4 ng/mL), according to the International Endocrine Society. Initially, he was treated with pimecrolimus cream without any effects. The skin problem partly resolved by using tacrolimus 0.1% ointment, which reduced the symptoms but for no longer than 1 to 2 weeks after discontinuing the treatment. Finally, a 0.6 μg/g calcitriol cream formulation applied to the affected areas twice a day over 10 days gradually and considerably ameliorated the skin lesions for up to 8 weeks (Fig 1, B). The vehicle of the cream formula did not ameliorate the skin symptoms.

Fig 1

Patient with atopic eyelid dermatitis. A, Before and B, 10 days after topical calcitriol (0.6 μg/g) treatment.

Discussion

Topical vitamin D derivatives are not listed as recommended therapeutic options in evidence-based guidelines for the treatment of AD. In fact, an unfavorable clinical outcome was described in a case report of a 2-year-old boy whose AD symptoms flared in response to topical application of calcipotriol (0.005%) for a mistaken diagnosis of psoriasis. In addition, investigations in mouse models found that AD can be induced by topical application of vitamin D3 analogues at doses corresponding to commercially available calcitriol or calcipotriol preparations used in the therapy of psoriasis patients.6, 7 Mechanistically, topically applied calcitriol at a concentration of 3 μg/g or its noncalcemic synthetic counterpart, calcipotriol, in an equivalent therapeutic dose of 50 μg/g induced interleukin 4 and thymic stromal lymphopoietin expression in epidermal keratinocytes, both representing pivotal cytokines involved in the pathophysiology of AD.6, 7 The mechanistic link for the observed difference between improvement of skin scores by systemic vitamin D supplementation and the reverse effect through topical vitamin D application in AD patients is widely unclear. Although it is known that vitamin D can exert immunoregulatory effects, a possible stimulation of keratinocytes and dendritic cells by topical application of calcitriol in a commercially available concentration (3 μg/g) may override the immunomodulatory action of 1,25-dihydroxyvitamin D3, thereby promoting a pro-allergic milieu in this disease. In fact, because topically applied calcitriol (0.6 μg/g) did not lead to worsening of AD skin symptoms in our case, we speculate that this low-dose treatment did not induce AD-relevant proinflammatory cytokines but rather restored a normal cytokine balance resulting in improvement of the skin lesions. This finding is in line with the assumption of Paracelsus that “All things are poison, and nothing is without poison: the dose alone makes a thing not poison.”

Future studies are needed to confirm our findings in a larger group of AD patients by a more objective evaluation (eg, SCORing index of AD), especially in those with involvement of vulnerable and sensitive areas of the body such as the face for which long-term treatment with conventional topical corticosteroids is contraindicated.