Giant Porokeratosis: New Topical Therapy Shows Promise
Publication Title: A 12-year expanding pink plaque on the chest
Summary
- Question
- This study examined the case of a 95-year-old man with a persistent, expanding pink plaque on his chest over 12 years. The researchers sought to identify the diagnosis and investigate the underlying genetic cause of this condition.
- Why it Matters
- Understanding the genetic and pathological basis of rare skin disorders like giant porokeratosis is essential for improving diagnostic accuracy and treatment options. Porokeratosis is considered a premalignant condition, meaning it has the potential to develop into skin cancer, with a reported malignant transformation rate of 7.5%. Early identification and effective treatment can help prevent this progression. This study also highlights the potential of novel therapies targeting specific genetic pathways, which could benefit patients with similar disorders.
- Methods
- The researchers conducted a clinical examination and performed multiple skin biopsies on the patient’s lesion over a 12-year period. Histological analysis revealed hallmark features of porokeratosis, such as cornoid lamellae (a distinctive layer of abnormal skin cells) and inflammation. They performed whole-exome sequencing, a technique used to analyze the DNA of protein-coding genes, comparing samples from the affected skin tissue and the patient’s blood to identify genetic mutations specific to the lesion.
- Key Findings
- The researchers diagnosed the patient with giant porokeratosis, a rare variant of porokeratosis that can grow to an unusually large size. Genetic testing revealed two somatic mutations in the MVK gene (mevalonate kinase) present only in the affected skin tissue, not in the patient’s blood. These mutations impact the mevalonate pathway, which is essential for producing cholesterol and other molecules critical for skin cell function and integrity. Previous treatments, including topical medications and phototherapy, failed to improve the condition. However, the researchers found that applying a combination of topical cholesterol and lovastatin (a drug that inhibits a key enzyme in cholesterol production) led to significant improvement in the plaque’s redness and itchiness after two months.
- Implications
- The findings confirm that mutations in the mevalonate pathway play a central role in the development of porokeratosis, emphasizing the importance of targeted therapies. The successful use of cholesterol/lovastatin treatment suggests a promising new option for managing porokeratosis and potentially other skin conditions linked to genetic defects in lipid metabolism. This research provides valuable insights for dermatologists and geneticists, while also offering hope for patients with challenging skin diseases.
- Next Steps
- The authors recommend further studies to evaluate the long-term effectiveness and safety of topical cholesterol/lovastatin treatment in larger patient populations with porokeratosis. Additionally, they suggest investigating the broader applicability of this therapy for other skin disorders caused by lipid metabolism abnormalities.
- Funding Information
- This research was not supported by any specific funding sources as stated in the paper. Yale University also provided funding and support for this research.
Full Citation
Etaee F, Castiglione F, Jiang X, Hu R, Galan A, Choate K, Vesely M. A 12-year expanding pink plaque on the chest. JAAD Case Reports 2026, 70: 86-89. PMID: 41798138, PMCID: PMC12966874, DOI: 10.1016/j.jdcr.2025.11.058.
This AI-assisted summary has been reviewed and approved by at least one of the study's authors to ensure it accurately reflects the research.
Authors
Farshid Etaee
First AuthorMatthew Vesely, MD, PhD
Last AuthorAssistant Professor of Dermatology