Topical cholesterol/lovastatin for the treatment of porokeratosis: A pathogenesis-directed therapy.
Administration, Cutaneous
Adult
Anticholesteremic Agents
/ administration & dosage
Carboxy-Lyases
/ genetics
Child, Preschool
Cholesterol
/ administration & dosage
Drug Combinations
Genotype
Humans
Lovastatin
/ administration & dosage
Middle Aged
Mutation
Ointments
Phosphotransferases (Phosphate Group Acceptor)
/ genetics
Porokeratosis
/ drug therapy
Young Adult
cholesterol
disseminated superficial actinic porokeratosis
genetic skin diseases
genetics
linear porokeratosis
medical dermatology
mevalonate pathway
pediatric dermatology
porokeratosis
statins
therapy
topical therapy
Journal
Journal of the American Academy of Dermatology
ISSN: 1097-6787
Titre abrégé: J Am Acad Dermatol
Pays: United States
ID NLM: 7907132
Informations de publication
Date de publication:
Jan 2020
Jan 2020
Historique:
received:
10
06
2019
revised:
13
08
2019
accepted:
20
08
2019
pubmed:
27
8
2019
medline:
1
7
2020
entrez:
27
8
2019
Statut:
ppublish
Résumé
Porokeratosis is associated with mevalonate pathway gene mutations. Therapeutic options are few and often limited in efficacy. We hypothesized that topical therapy that aims to replenish cholesterol, an essential mevalonate pathway end-product, and block the accumulation of mevalonate pathway toxic metabolites could alleviate porokeratosis. To study the efficacy of topical cholesterol/lovastatin in different variants of porokeratosis. We enrolled a series of 5 porokeratosis patients,1 with disseminated superficial actinic porokeratosis, 2 with porokeratosis palmaris et plantaris disseminata, and 2 with linear porokeratosis. Patients were genotyped before initiation of therapy. Patients then applied topical cholesterol/lovastatin twice daily to a unilaterally defined treatment area for up to 3 months. The response was evaluated and patients photographed at every visit. Three patients had MVD mutations, and 2 patients had PMVK mutations. Treatment with topical cholesterol/lovastatin (but not cholesterol alone) resulted in near complete clearance of disseminated superficial actinic porokeratosis lesions after 4 weeks of therapy and moderate improvement of porokeratosis palmaris et plantaris disseminata lesions and linear porokeratosis lesions. There were no adverse events. Case series design with a small number of patients. Topical cholesterol/lovastatin is an effective and well-tolerated therapy for porokeratosis that underscores the utility of a pathogenesis-based therapy that replaces deficient end products and prevents accumulation of potentially toxic precursors.
Sections du résumé
BACKGROUND
BACKGROUND
Porokeratosis is associated with mevalonate pathway gene mutations. Therapeutic options are few and often limited in efficacy. We hypothesized that topical therapy that aims to replenish cholesterol, an essential mevalonate pathway end-product, and block the accumulation of mevalonate pathway toxic metabolites could alleviate porokeratosis.
OBJECTIVE
OBJECTIVE
To study the efficacy of topical cholesterol/lovastatin in different variants of porokeratosis.
METHODS
METHODS
We enrolled a series of 5 porokeratosis patients,1 with disseminated superficial actinic porokeratosis, 2 with porokeratosis palmaris et plantaris disseminata, and 2 with linear porokeratosis. Patients were genotyped before initiation of therapy. Patients then applied topical cholesterol/lovastatin twice daily to a unilaterally defined treatment area for up to 3 months. The response was evaluated and patients photographed at every visit.
RESULTS
RESULTS
Three patients had MVD mutations, and 2 patients had PMVK mutations. Treatment with topical cholesterol/lovastatin (but not cholesterol alone) resulted in near complete clearance of disseminated superficial actinic porokeratosis lesions after 4 weeks of therapy and moderate improvement of porokeratosis palmaris et plantaris disseminata lesions and linear porokeratosis lesions. There were no adverse events.
LIMITATIONS
CONCLUSIONS
Case series design with a small number of patients.
CONCLUSION
CONCLUSIONS
Topical cholesterol/lovastatin is an effective and well-tolerated therapy for porokeratosis that underscores the utility of a pathogenesis-based therapy that replaces deficient end products and prevents accumulation of potentially toxic precursors.
Identifiants
pubmed: 31449901
pii: S0190-9622(19)32648-9
doi: 10.1016/j.jaad.2019.08.043
pmc: PMC7039698
mid: NIHMS1558770
pii:
doi:
Substances chimiques
Anticholesteremic Agents
0
Drug Combinations
0
Ointments
0
Cholesterol
97C5T2UQ7J
Lovastatin
9LHU78OQFD
Phosphotransferases (Phosphate Group Acceptor)
EC 2.7.4.-
phosphomevalonate kinase
EC 2.7.4.2
Carboxy-Lyases
EC 4.1.1.-
pyrophosphomevalonate decarboxylase
EC 4.1.1.33
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
123-131Subventions
Organisme : NIAMS NIH HHS
ID : R01 AR071491
Pays : United States
Organisme : NIAMS NIH HHS
ID : T32 AR007016
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM007205
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001863
Pays : United States
Commentaires et corrections
Type : CommentIn
Type : CommentIn
Informations de copyright
Copyright © 2019. Published by Elsevier Inc.
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