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ATYPICAL SKIN RASHES: Molecular profiling may guide therapy.


CHICAGO -- Although at a relatively early stage of research, molecular profiling is showing promise for personalizing treatment of rashes of unknown origin that do not respond to conventional therapies, according to research that was described at the annual meeting of the Society for Investigative Dermatology.

"We now have several cases that suggest single-cell molecular profiling can provide treatment guidance for atypical rashes, providing an opportunity for a rational treatment choice rather than just improvising in a difficult population," reported Raymond Cho, MD, PhD, of the department of dermatology at the University of California, San Francisco.

Based on a growing cohort of patients with atypical rashes, one goal is to develop "a library of molecular fingerprints" for classifying rashes that are atypical when defined by morphology, histopathology, or therapeutic response, according to Dr. Cho.

"The big focus now is on expanding this patient cohort. We want to move from anecdotal cases to a larger patient population with which we can statistically prove that we can nominate the best first-line therapy through this approach," he explained.

In describing work he is performing in collaboration with Jeffrey Cheng, MD, also with the department of dermatology at UCSF, Dr. Cho said the profiles are based on RNA sequencing from single immune cells and epitope measurements. Work already performed in rashes of known etiology supports the approach. For example, the profile for atopic dermatitis includes elevated expression of interleukin (IL)-4 and IL-13, whereas that of psoriasis includes elevated expression of IL-17, which fit with the expected molecular signatures of these diseases.

To be considered for inclusion in the cohort of atypical rashes, patients are required to have an idiopathic skin lesion of at least 6 months' duration with at least two atypical features defined by such characteristics as morphology or location. Many of these patients have already consulted with multiple providers, have undergone multiple biopsies without a diagnosis, and have failed common treatments, such as steroids.

Examples selected from this cohort have already supported the premise that molecular profiles are relevant to treatment choice. Dr. Cho described one patient with unremitting generalized pruritus and another with nodular lesions on the legs. Both had symptoms of long duration that had failed multiple treatments.

In both cases, immune cell profiling identified lesions high in IL-13 expression. Both achieved complete or near complete resolution of their rash and symptoms when treated with dupilumab, a biologic that targets the IL-13 pathway. In one patient with a large symptom burden, Dr. Cho described the response as "remarkable."

There are more than 40 patients in the expanding cohort, according to Dr. Cho, who emphasized that this work is timely because of "the armamentarium of immunomodulatory drugs that are coming on line." He said this type of drug development in dermatology is the basis for a potential paradigm shift.

"Personalized therapy has been used in clinical oncology for almost 10 years now, but this is an approach that needs to find a home in our specialty as well," Dr. Cho said. He cited data suggesting that nearly 15% of rashes are atypical and represent a major source of frustration to both patients and clinicians when conventional treatments fail.

Asked about cost, he acknowledged that the molecular profiling that he and Dr. Cheng are performing is expensive at the current time, but "we are hopeful that we can find cheaper markers and technologies" to bring this cost down. However, he noted that undiagnosed rashes consume a great deal of time of effort from clinicians while generating significant morbidity for patients, which is justifying novel strategies to find effective therapies.

"These are not happy patients," Dr. Cho said. Although there are technical challenges for building a molecular library that has practical utility across the substantial heterogeneity of idiopathic rashes, he suggested that a larger patient sample is considered one of the important steps toward overcoming hurdles.

Dr. Cho reported no potential conflicts of interest.

Dr. Cho discussed these results in an interview in a recent episode of Dermatology Weekly at


Caption: Dr. Jeffrey Cheng (left) and Dr. Raymond Cho (right) in their lab at UCSF.

Caption: Dr. Raymond Cho said that one goal is to develop "a library of molecular fingerprints" for classifying atypical rashes.

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Author:Bosworth, Ted
Publication:Dermatology News
Date:Aug 1, 2019
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