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In a recent case report, a novel immunophenotyping platform featuring high-parameter flow cytometry of peripheral blood mononuclear cells (PBMCs) enabled physicians to discover a unique skin disease and treat a unique case of recalcitrant erythroderma using targeted dual biologic therapy. The minimally invasive diagnostic platform also identified immune signatures of additional erythroderma subtypes, and the authors said that one day, it may allow personalized treatment of many systemic inflammatory skin diseases.

“We had a patient who had a form of whole-body redness that wasn’t responding to traditional therapies,” principal investigator Shawn G. Kwatra, MD, told Medscape Dermatology in an interview. He is a professor and chair of dermatology at the University of Maryland Medical School, Baltimore. The article appeared online on January 14 in Scientific Reports.

Probing PBMCs

Despite an extensive medical workup, the 68-year-old male patient’s extensive redness, itching, and burning resisted commonly used treatments including steroids, oral immunosuppressants, and the tumor necrosis factor blocker adalimumab. To better profile the patient’s disease, investigators created a novel blood test that examines PBMCs, which Kwatra said are among the most effective markers of underlying immunology.

Investigators performed functional immunophenotyping via high-parameter flow cytometry on PBMCs stimulated with pan-T stimulation to characterize T-cell differentiation in the patient’s blood and that of several controls. Performing flow cytometry on PBMCs stained with antigen-presenting cell-focused markers allowed characterization of macrophages, monocytes, and dendritic cells. To further examine granulocyte populations, researchers performed flow cytometric analysis on whole blood as well.

Analysis revealed that the index patient had combined Th2 and Th17 dysregulation leading to increased levels of interleukin (IL)-13 and IL-17. His stimulated T cells expressed 15.11% more IL-13 and 6.21% more IL-17 than three healthy control individuals. Levels of these cytokines also were elevated when compared with one patient each with pityriasis rubra pilaris and Sézary syndrome.

Compared with healthy and erythrodermic control individuals, the patient’s CD3+ IL-4– and IL-13–secreting cells showed an elevated population of clonal gamma V delta 2 T cells (3.13%). The patient had the highest level of clonal gamma V delta 1 T cells (46.80%) and gamma V delta 2 T cells (1.21%) among CD3+ IL-17–producing cells. “These findings suggest that [gamma V delta] T cells are a likely source of the pathogenic IL-13 and IL-17 in the index patient,” the authors wrote. Whole-genome sequencing of PBMCs and immunostaining of skin biopsies validated these findings.

Targeting Cytokines

Treatment with dupilumab, which targets IL-4 and IL-13, and secukinumab, which targets IL-17, cleared the patient’s skin symptoms by eliminating underlying cytokine dysregulation at its sources. Based on the immunophenotyping platform’s success in this case, said Kwatra, it could prove invaluable to physicians treating a broader array of common and uncommon inflammatory skin diseases.

As the availability of monoclonal antibodies and small-molecule inhibitors for inflammatory skin diseases continues to grow, he said, “it helps to use a precision medicine approach so that you can get more information about the specific pattern of inflammation in individual patients.”

Part of the platform’s appeal is that it is much less invasive than skin biopsy and can reveal unique etiologies of systemic inflammation, Kwatra said. He has seen many patients with eczema whose skin biopsy appears to show a psoriasiform dermatitis or psoriasis. Chronic atopic dermatitis leads to skin thickening and lichenification that looks like psoriasis, Kwatra explained. “And this type of test is able to identify the systemic inflammation that’s driving the skin disease you’re seeing.”

The test also may prove useful, said Kwatra, for monitoring therapeutic response and discovering new skin diseases. At present, he and his colleagues are customizing the patented platform to map the circulating systemic blood signatures of all inflammatory skin diseases, focusing on cytokines of interest targeted by newer therapeutics. With funding from the National Institutes of Health (NIH), the Society for Investigative Dermatology (SID), and other partners, this project should be completed within the next few years, Kwatra said. Investigators plan to share early data — along with flow cytometric analysis of immune dysregulation in multiple chronic pruritic diseases — at the SID Annual Meeting in May.

The study was supported by an NIH grant.

John Jesitus is a Denver-based freelance medical writer and editor.