Diffuse normolipemic plane xanthoma and hepatitis C: chance?

Souza, Maria Carolina Casa; Martins, Paulo Henrique; Vivian, Analú; Luzzatto, Laura

doi:10.1016/j.abd.2019.08.026

Cited by 2 publications

(2 citation statements)

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“…Pathologically, there were fewer foam cells and inflammatory cells in the dermis ( Figure 1E ). Although oral lipid-lowering agents generally show good results in patients with DPX, there is no clinically effective treatment for DNPX ( 12 , 14 ). Furthermore, many statins are only approved for use in patients of 8–10 years of age ( 29 ).…”

Section: Discussionmentioning

confidence: 99%

“…Most patients with DPX present elevated blood lipid levels, and treatment with oral lipid-lowering agents has promising results ( 12 , 13 ). However, a small number of patients with DPX show normal blood lipid levels, known as diffuse normolipemic plane xanthoma (DNPX), for which no effective treatment is available ( 5 , 14 ). Therefore, it is important to develop new therapeutic strategies.…”

Section: Introductionmentioning

confidence: 99%

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Topical Simvastatin Improves Lesions of Diffuse Normolipemic Plane Xanthoma by Inhibiting Foam Cell Pyroptosis

et al. 2022

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Xanthoma pathogenesis is speculated to be associated with oxidized low-density lipoprotein (ox-LDL) deposition, although this remains unclear. Most patients with diffuse plane xanthomas present elevated blood lipid levels, and they benefit from treatment with oral lipid-lowering agents. However, there is no available treatment for diffuse normolipemic plane xanthoma (DNPX). In this study, for the first time, we used a topical simvastatin ointment to treat DNPX in three pediatric patients and observed favorable results. Immunofluorescence staining showed that the pyroptotic pathway was significantly attenuated after topical simvastatin application on the skin lesions of the patients. As ox-LDL deposition was observed in the lesions, we used ox-LDL to build a foam cell model in vitro. In the ox-LDL-induced foam cell formation, simvastatin consistently inhibited pyroptotic activation and inflammation in the macrophages. Additionally, the overexpression of nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) or 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase (HMGCR), the known target of statins, reversed the effects of simvastatin. Moreover, gasdermin D (GSDMD) or HMGCR knockdown inhibited ox-LDL-induced pyroptosis. Furthermore, the immunoprecipitation results confirmed the interaction between NLRP3 and HMGCR, and this interaction was inhibited by simvastatin. In conclusion, we demonstrated that topical application of simvastatin ointment might be a promising treatment for DNPX skin lesions and that this therapeutic effect may be related to pyroptosis inhibition via HMGCR inhibition in foam cells. Moreover, xanthoma pathogenesis might be associated with ox-LDL deposition and inflammation.

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Section: Discussionmentioning

confidence: 99%