DOCTORS USUALLY diagnose skin rashes by eye. Some examine the physical appearance of a skin sample under a microscope and it may work for common skin conditions but many other rashes can be hard to distinguish from one another. The treatment for skin rashes is often hit and miss (based on my experience), with obvious result. But at the molecular level, the differences between rashes are more exact.
Molecular testing of skin rashes isn’t a common practice because of technological limitations. Using a new approach, scientists were able to analyze the genetic profiles of skin rashes and quantitatively diagnose their root causes.
Recent technological advances, called single-cell RNA sequencing, have enabled scientists to preserve the identity of each type of cell that lives in the skin. Instead of averaging the genetic signatures across all cell types in bulk, single-cell RNA sequencing analyses allow each cell to preserve its unique characteristics.
Using this approach, researchers isolated over 158,000 immune cells from the skin samples of 31 patients. They measured the activity of about 1,000 genes from each of those cells to create detailed molecular fingerprints for each patient. By analyzing these fingerprints, they were able to pinpoint the genetic abnormalities unique to the immune cells residing in each rash type. This allowed them to quantitatively diagnose otherwise visually ambiguous rashes.
To make the approach available to clinicians and scientists, an open source web database called RashX that contains the genetic fingerprints of different rashes was developed. This database allows clinicians to compare the genetic profile of their patients’ rashes to similar profiles in the database. A closely matching genetic fingerprint could yield clues as to what caused a patient’s rash and lead to potential treatment options.
The rapid development of drugs that target the immune system in recent years has flooded doctors with difficult treatment decisions for individual patients. For example, while certain drugs that act on the immune system are known to work well for conditions like psoriasis or eczema, many patients have atypical rashes that cannot be precisely diagnosed.
An open source database could help enable clinicians to profile and diagnose these rashes, providing a stepping stone to choose a suitable treatment. Chronic inflammatory diseases that affect organs other than the skin share similar genetic abnormalities.
Lab tests that can illuminate the root causes of skin diseases can likely be expanded to many other conditions. The RashX project initially focused on just two very common types of rashes, psoriasis and eczema. It is unknown whether other types of rashes will have similar genetic profiles to psoriasis and eczema or instead have their own unique fingerprints. But RashX is a living web resource that will grow more useful as more scientists collaborate and contribute new data. The lab is also working to simplify the process of developing genetic profiles of rashes to make participating in this area of research more accessible for clinics around the world. With more data, projects like RashX will make precision testing for rashes an essential next step in diagnosis and treatment. (By Manny Palomar, PhD, EV Mail July 25-31, 2022 Issue)
