Appearance of lentigines in psoriasis patients treated with apremilast

Abstract

Fig 1. Lentigines restricted to areas of previous psoriatic plaques 5 years after their occurrence.

Cutaneous hyperpigmentation induced by apremilast

“…demonstrated that the use of topical rolipram, a PDE4 inhibitor, alone or in combination with forskolin, in C57bl6e/e K14 SCF mice carrying the red hair phenotype can induce robust darkening of the skin in the absence of sun exposure . Recently, apremilast has been acknowledged for post‐inflammatory lentiginosis after treatment for psoriasis, as well . These data might account for the increased dark hyper pigmentation in our patient as direct effect of PDE4 inhibition by apremilast, not only in inflammatory cells but also in melanocytes.…”

Apremilast in psoriasis and beyond: Big hopes on a small molecule

“…[ 54 ] Rare side effects include diverticulitis, hyperpigmentation, postinflammatory lentiginosis, purpura annularis telangiectodes of Majocchi, persistent epiphora, and fanconi syndrome. [ 55 56 57 58 59 60 ] Apremilast is an anti-inflammatory drug and does not cause immunosuppression. Laboratory parameters also did not show any clinically meaningful changes with apremilast treatment.…”

Multiple lentigines arising on resolving psoriatic plaques after treatment with apremilast

“…In their report of lentigines during apremilast treatment, Sfecci et al . hypothesized that the inhibition of microphthalmia‐associated transcription factor, a transcription factor of melanogenesis and melanocyte differentiation and proliferation, by phosphodiesterase‐4 (PDE4) could be limited when apremilast inhibits PDE4 in turn, thus stimulating melanogenesis and melanocyte differentiation . In our opinion, the rapid decrease in proinflammatory cytokines caused by successful psoriasis treatments could suppress a brake on melanogenesis signalling pathways inside psoriatic plaques, leading to a burst of pigmentation and the development of lentigines once the plaques resolve.…”

“…Hyperpigmented lesions confined to resolving psoriatic plaques were described initially after psoralen ultraviolet A treatment, then later in patients with or without history of previous phototherapy taking other multiple therapies, such as topical calcipotriol or systemic biologic agents, and most recently, during treatment with apremilast . Apremilast is a phosphodiesterase 4 inhibitor approved for the treatment of psoriasis and psoriatic arthritis, which induces the elevation of intracellular cyclic adenosine monophosphate, causing a decrease in production of tumour necrosis factor (TNF)‐α and other proinflammatory cytokines, such as interleukin (IL)‐1α, as well as upregulation of anti‐inflammatory cytokines such as IL‐10.…”