Olmsted syndrome is a rare disease most frequently caused by mutations in TRPV3. For some patients, it is caused by MBTPS2 mutations. It is characterized by palmoplantar keratoderma (PPK) as well as periorificial hyperkeratotic plaques. The condition currently has no approved effective treatment.
But researchers believe that a cancer drug called erlotinib could be a new option for pediatric Olmsted syndrome patients. Currently this drug is used to treat adults who have PPK but it has never been used for youth.
A recent study published in JAMA Dermatology examined this possibility.
Alain Hovnanian and his team investigated two cancer drugs as a treatment for Olmsted. These therapies, sirolimus and erlotinib, were studied in 4 children diagnosed with the condition who had a median age of seven. The study was multicenter, taking place in the United States and Brazil. It spanned from 2017-2018.
Two of the patients (who were twins) were given sirolimus first. These children had improvements in periorificial hyperkeratotic plaques, pain scores, erythema, and pruritus. These participants were switched to erlotinib after nine months of sirolimus. After the switch, PPK was resolved. The second child was able to walk after just two weeks of the treatment.
The other two participants were only ever given erlotinib. PPK was resolved and the quality of life of these patients was improved. These improvements were fast and dramatic.
As the outcomes from all four of these patients were positive overall, researchers are hopeful that both erlotinib and sirolimus could be a treatment option for Olmsted syndrome patients in the future.
A Second Investigation
A second study conducted by Christine Bodemer and Céline Greco from 2018 to 2019 studied erlotinib in teenage Olmsted syndrome patients.
The trial included three patients, two who were brothers. All had the condition since birth. They suffered from anorexia, growth delay, insomnia, pain, and erythromelalgia. They had difficulties walking or were unable to walk and faced depression and social isolation.
This research team wanted to evaluate whether a dose of erlotinib that is lower than typically used for cancer could aid in Olmsted syndrome when it is caused by the TRPV3 mutation.
All of the participants had resolved hyperkatosis, pain, anorexia, as well as insomnia in just three months of treatment. Their growth was improved and they were able to walk. These results were sustained for 12 months. No major AEs were documented. Researchers expect that a continuous dose of the drug will be needed to maintain remission.
There are of course limitations to these investigations, primarily surrounding sample size and the lack of a control group. Additionally, inquiry is needed regarding the effect of the treatment on Olmsted syndrome patients who have a different kind of mutation. Furthermore, studies should have a longer follow-up period so that long-term safety and efficacy can be assessed. A continuing challenge is the fact that their has yet to be a standardized rating scale created for Olmsted.
Nonetheless, the scientific community is hopeful and excited about these promising findings. These small studies have shown that using erlotinib to target EGFR transactivation can lead to the clinical remission of Olmsted syndrome patients. As a result, researchers believe that erlotinib may be able to also benefit those who have different keratinization disorders that have similar pathology to the syndrome.
Stay tuned to hear future updates on these investigative therapies!
You can read more about these studies here.