The long-term risk of lymphoma and skin cancer did not increase after topical calcineurin inhibitor use and phototherapy in a cohort of 25,694 patients with vitiligo.

BACKGROUND: Topical calcineurin inhibitors have been used to treat vitiligo, either alone or in combination with phototherapy; however, the long-term safety of these agents remains controversial. OBJECTIVE: To investigate the risk of lymphoma and skin cancer in vitiligo patients who received topical calcineurin inhibitors or phototherapy. METHODS: A multicenter retrospective cohort study of 25,694 vitiligo patients who received topical calcineurin inhibitors or phototherapy for 6 weeks or more between 2001 and 2019 was performed. Cumulative doses of topical calcineurin inhibitors and total phototherapy sessions were determined. Outcomes were the development of lymphoma or skin cancer after enrollment, confirmed through chart review and pathology reports. RESULTS: During 95,203 person-years, 13 cases of lymphoma, 22 of actinic keratosis, 15 of nonmelanoma skin cancer, and 5 of melanoma were observed. The risk of lymphoma and skin cancer was not significantly increased by topical calcineurin inhibitor dose or phototherapy sessions. The interaction between the topical calcineurin inhibitors and phototherapy was not associated with an increased risk of skin cancer. LIMITATIONS: Retrospective study, individual follow-up duration less than 4 years, and no adjustment for comorbidities and medication history. Not generalizable to other races. CONCLUSION: The long-term risk of skin cancer or lymphoma was not associated with the use of topical calcineurin inhibitors, phototherapy, and both treatments in combination in patients with vitiligo.

Fibroblasts and ascorbate regulate epidermalization in reconstructed human epidermis.

Skin equivalent model provides a new investigating system to study the role of extracellular matrix and dermal factors such as collagen, basement membrane components and fibroblasts (Fb) which contribute to cell-cell and cell-matrix interactions. Although basement membrane factors is known to play an important role in epidermal differentiation and epidermal-matrix adhesion, comparative effects of these extracellular matrix and dermal factors on the reconstruction of epidermis are little known. In this study, we investigated effects of type I collagen (Coll I), type IV collagen plus laminin (LAM) coated Coll I (Coll IV+LAM), and human Fb enriched Coll I (Coll I+Fb) on epidermal reconstruction. When human keratinocytes were cultured on three different gels containing Coll I, Coll IV+LAM and Coll I+Fb, basal keratinocytes were cuboidal and perpendicular to the dermo-epidermal junction only in the gel containing Coll I+Fb. Proliferation marker expression was prominent and differentiation marker expression was similar with those of normal skin in the gel containing Coll I+Fb than in the other gel models. Since ascorbate is suspected to exert an effect as a modulator of proliferation and differentiation in keratinocytes, we tested the effects of ascorbate on human epidermis reconstruction. When 25 microg/ml ascorbate was added, disordered arrangement of epidermis was disappeared and differentiation marker expression was similar with its expression in normal skin. These data indicate that human Fb and a modulator of proliferation and differentiation such as ascorbate are essential for epidermalization in reconstructed epidermis.