A case has been reported of generalized pustular psoriasis (GPP) in a 2-year-old girl for whom results of whole exome sequencing (WES) and RNA sequencing (RNA-seq) were useful in reflecting her response to treatment with cyclosporin and etanercept.

The report, published in Experimental Dermatology, noted that the sequencing techniques revealed the downregulation of genes associated with the interleukin (IL)-1/IL-6 inflammatory axis, which is thought to underlie the pathogenesis of GPP.

“Systemic biological agents including anti-TNF-α, anti-IL-17, anti-IL-12/IL-23, anti-IL1R, anti-IL1β and anti-IL-36R act as novel treatment methods for GPP,” the authors wrote. “We report this case to demonstrate WES and RNA-seq in combination could come in handy in reaching a precise diagnosis and in evaluating or even predicting the molecular alterations underlying clinical treatment effectiveness.”

The research team collected peripheral blood specimens from the patient and tailored a gene panel for WES variant filtering for GPP prior to conducting WES and Sanger sequencing.

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The girl was treated first with oral cyclosporin, to which she showed a partial response. The treatment was switched to etanercept, an anti-TNFα inhibitor, for 3 weeks, leading to nearly total remission after 2 weeks.

Peripheral blood samples were taken before and after each of the 2 treatments and from 2 healthy control patients. RNA sequencing was employed to assess the molecular changes at the transcriptome level in response to the treatment.

The results showed that the transcriptomic profile of the samples after treatment with etanercept were much more similar to that of the control samples than those before etanercept therapy, and the same was observed with the samples before and after the subsequent cyclosporin therapy.

The authors concluded that the 2 sequencing techniques could be advantageous in achieving precise diagnoses and in evaluating the molecular alterations in response to treatments for GPP.


Lin YC, Jeng YC, Aala WJF, et al. Transcriptomic responses of peripheral blood mononuclear cells to cyclosporin and etanercept in a female infant with juvenile generalized pustular psoriasisExp Dermatol. Published online May 17, 2023. doi:10.1111/exd.14835