Rationale for the Development of Speckled Hyperpigmentation in the Areas of Psoriatic Plaques after Treatment with Biologic Agents

Cesare, Antonella Di; Fargnoli, Maria Concetta; Marinucci, Alessandro; Peris, Ketty

doi:10.1038/jid.2014.297

Cited by 15 publications

(16 citation statements)

References 16 publications

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“…Moreover, an increase of Tyr and BMP-4 was assessed in responder patients after 16 weeks of anti-TNF-α therapy, whereas levels similar to baseline were encountered for non responder subjects. As hypothesized by Di Cesare et al (8), high levels of melanogenesis markers induced by the treatment with TNF-α blockers could increase pigmentation signaling pathway. A possible role of BMP-4 in psoriatic post-inflammatory hyper-pigmentation has not been explored, even though controversial data exist on this marker in the process of melanogenesis (6,13).…”

Section: Discussionmentioning

confidence: 83%

“…Synergistic action of these mediators down-regulates the pigmentation signaling pathway and melanin production (4)(5)(6). Previous studies have reported that primary human melanocytes respond to IL-17 and/or TNF-α stimulation forming clusters and modulating the expression of melanogenesis markers [e.g., microphthalmia-associated transcription factor (MITF) and tyrosinase (Tyr)] (7,8). Indeed, therapeutic neutralization of IL-17 and TNF-α with biologic agents is able to increase pigmentation signaling in the areas corresponding to the psoriatic plaques (8).…”

Section: Introductionmentioning

confidence: 99%

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Possible role of BMP‑4 in the hyper‑pigmentation of psoriatic plaques after anti‑TNF‑α treatment

et al. 2019

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Psoriasis over-expresses several inflammatory mediators, which impacts the activity of melanocytes. Tyrosinase (Tyr) and microphthalmia-associated transcription factor (MITF) are the primary regulators of melanogenesis. Furthermore, bone morphogenetic proteins (BMPs) modulate various pathobiologic processes including inflammation, melanogenesis and melanomagenesis. To determine the association between psoriasis and melanogenesis, psoriatic lesional skin was screened through gene expression, immunohistochemistry, immunogold staining and melanin content assays. The present study detected a decreased expression of Tyr, MITF and BMP-4 in psoriatic lesional skin compared with healthy skin. Tyr, BMP-4 and melanin content were also evaluated in the psoriatic lesional skin of patients receiving adalimumab therapy, before and after 16 weeks of treatment. TNF-α blockade modulated the Tyr, BMP-4 and melanin content of the patient skin lesions, which supported the hypothesis that hyper-pigmentation may occur in areas of psoriatic plaque after biological treatment. The present study confirmed the influence of the psoriatic pro-inflammatory network on melanogenesis, exerting an inhibitory effect mediated by TNF-α. Furthermore, the results regarding BMP-4 in the present study add another important element to the mechanism of psoriasis.

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Section: Discussionmentioning

confidence: 83%

Section: Introductionmentioning

confidence: 99%

Possible role of BMP‑4 in the hyper‑pigmentation of psoriatic plaques after anti‑TNF‑α treatment

et al. 2019

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“…Psoriatic skin symptoms improved in this study, but PIH may have led participants to report lower subjective improvements as a result of dissatisfaction with their skin's appearance. PIH is commonly observed in the treatment of psoriasis, varies among patients, is transient and disappears over time . The DLQI assessments in this study were only made at baseline and week 8.…”

Section: Discussionmentioning

confidence: 99%

Comparison of indirubin concentrations in indigo naturalis ointment for psoriasis treatment: a randomized, double‐blind, dosage‐controlled trial

et al. 2017

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Summary Background Indigo naturalis and its refined formulation, Lindioil, are effective in treating psoriatic symptoms topically. Indirubin is the active ingredient in indigo naturalis. Objectives To determine the efficacy and safety of different concentrations of indirubin in Lindioil ointment for treating psoriasis. Methods In this randomized, double‐blind trial, adult patients presenting with chronic plaque psoriasis for > 1 year and with < 20% of the body surface area (BSA) affected were randomized to apply Lindioil ointment containing 200, 100, 50 or 10 μg g−1 of indirubin twice daily for 8 weeks followed by an additional 12‐week safety/extension period. The primary end point was the mean percentage change in Psoriasis Area and Severity Index (PASI) score along with the proportion of participants achieving 75% and 90% reductions in PASI scores (PASI 75 and PASI 90, respectively) from baseline to week 8. Results The results from week 8 revealed that the 200 μg g−1 group had the greatest reduction in PASI score [69·2%, 95% confidence interval (CI) 55·5–82·8], followed by the 100 μg g−1 group (63·1%, 95% CI 52·8–73·5), the 10 μg g−1 group (53·4%, 95% CI 42·8–64·0) and the 50 μg g−1 group (50·3%, 95% CI 37·4–63·2), with a between‐group comparison of P = 0·0445. The group with the highest proportion of the patients achieving PASI 75 (57%, P = 0·0474) and PASI 90 (30%, P = 0·0098) was the 200 μg g−1 group. No severe treatment‐related adverse events were reported during the 20‐week evaluation. Conclusions An amount of 200 μg g−1 of indirubin in Lindioil ointment is the most effective concentration studied so far for treating psoriasis topically, and is safe.

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“…Individual case reports with corticosteroids, calcipotriol, dithranol, coal tar solution and apremilast have also been published. More recently, it has been reported following biological therapy including adalimumab, infliximab, etanercept, ustekinumab and ixekizumab . We report ELRP in two first‐time users of methotrexate (MTX) therapy whose psoriasis previously healed with uniform pigmentation.…”

mentioning

confidence: 94%

“…It has been suggested to be a form of postinflammatory hyperpigmentation or an abnormal reaction to UV light with relative contributions of skin type, disease severity and genetic predisposition . A few authors have demonstrated release of a cytokine‐mediated brake on melanogenesis by anti‐tumour necrosis (TNF)α or anti‐interleukin‐17 agents, leading to activation of locally infiltrated melanocytes in psoriatic skin and melanin production . Similarly, induction of a negative feedback loop on the cyclic AMP pathway and inhibition of melanogenesis‐associated transcription factor by the phosphodiesterase‐4 inhibitor apremilast may stimulate melanogenesis .…”

mentioning

confidence: 99%

Methotrexate‐induced eruptive lentiginosis in resolving psoriasis: a phenomenon possibly dependent on cytokine modulation

Singh

Beniwal

2019

Clin Exp Dermatol

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Rationale for the Development of Speckled Hyperpigmentation in the Areas of Psoriatic Plaques after Treatment with Biologic Agents

Cited by 15 publications

References 16 publications

Possible role of BMP‑4 in the hyper‑pigmentation of psoriatic plaques after anti‑TNF‑α treatment

Possible role of BMP‑4 in the hyper‑pigmentation of psoriatic plaques after anti‑TNF‑α treatment

Comparison of indirubin concentrations in indigo naturalis ointment for psoriasis treatment: a randomized, double‐blind, dosage‐controlled trial

Methotrexate‐induced eruptive lentiginosis in resolving psoriasis: a phenomenon possibly dependent on cytokine modulation

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