Study identifies potential biomarkers for an increased risk of SCARs-related mortality

Researchers have identified biomarkers that might eventually be used to flag cancer patients with severe cutaneous adverse reactions (SCARs) at an increased risk of mortality.

In a retrospective study, elevated elafin, interleukin (IL)-6, and tumor necrosis factor (TNF)–alpha levels were significantly associated with a greater risk of all-cause mortality among hospitalized cancer patients who developed SCARs, which includes Stevens-Johnson syndrome, toxic epidermal necrolysis, and drug-induced hypersensitivity syndrome.

In the study, published in the Journal of the American Academy of Dermatology, Shoko Mori of the dermatology service at Memorial Sloan Kettering Cancer Center, New York, and coauthors looked at 49 cancer patients hospitalized (41) or treated at an urgent care center (8), between August 2016 and July 2017 who experienced a morbilliform rash. Overall, 27 patients had a simple morbilliform rash, without systemic involvement; 22 had a complex morbilliform rash with systemic involvement, including 9 with cutaneous manifestations of graft versus host disease (GVHD) and 13 with rashes secondary to drug exposure.

The majority of the patients had a hematologic malignancy (18 with a simple rash, and 16 with a complex rash); the rest had a solid organ malignancy (9 with a simple rash and 6 with a complex rash).

Nearly one-third (30.6%) of patients died within 6 months of having a dermatologic consultation. These patients showed significantly higher levels of serum elafin – a protein that is not detectable in normal skin but is overexpressed in wound healing and inflammatory disorders – as well as IL-6 and TNF-alpha, compared with patients who were alive at 6 months.

“While GVHD and drug-related SCARs are difficult to distinguish clinically, our results suggest that elafin may be a useful biomarker to identify patients with a suspected diagnosis of SCARs or GVHD who are at increased risk of death within 6 months,” the investigators wrote. “Given its broad anti-inflammatory activity, elafin’s potential as a therapeutic agent for SCARs should be further explored.”

They noted that elevated TNF-alpha levels pointed to another potential therapeutic target for SCARs among patients undergoing treatment for cancer. Patients who died were also less likely to have elevated bilirubin level relative to baseline than patients who survived past 6 months.

The patients with a complex morbilliform rash caused by drug exposure had significantly higher median levels of IL-10 and IL-6, compared with those with a complex rash related to GVHD or with a simple rash. “Thought to originate from activated keratinocytes in TEN [toxic epidermal necrolysis], elevated IL-10 may reflect a defense mechanism against drug-specific cytotoxic T cells that are activated during the disease process,” the authors wrote.

Patients with complex rash also had a significantly higher median white blood cell count and higher median values for all cytokines, compared with the simple rash group, although only differences in TNF-alpha levels were statistically significant.

“A larger, prospective study examining the association of cytokines with SCARs is needed, as well as longitudinal assessment of cytokine levels to assess their prognostic significance,” the authors wrote. “This exploratory analysis presents potential therapeutic targets in a high-risk patient population, for whom a ‘complex’ rash can disrupt and delay treatment of underlying disease.”

The study was partly funded by the National Cancer Institute/National Institutes of Health via a grant to the Memorial Sloan Kettering Cancer Center. One author declared support from a Dermatology Foundation Career Development Award.

SOURCE: Mori S et al. J Am Acad Dermatol, 2018 October 26. doi: 10.1016/j.jaad.2018.10.039.

Researchers have identified biomarkers that might eventually be used to flag cancer patients with severe cutaneous adverse reactions (SCARs) at an increased risk of mortality.

In a retrospective study, elevated elafin, interleukin (IL)-6, and tumor necrosis factor (TNF)–alpha levels were significantly associated with a greater risk of all-cause mortality among hospitalized cancer patients who developed SCARs, which includes Stevens-Johnson syndrome, toxic epidermal necrolysis, and drug-induced hypersensitivity syndrome.

In the study, published in the Journal of the American Academy of Dermatology, Shoko Mori of the dermatology service at Memorial Sloan Kettering Cancer Center, New York, and coauthors looked at 49 cancer patients hospitalized (41) or treated at an urgent care center (8), between August 2016 and July 2017 who experienced a morbilliform rash. Overall, 27 patients had a simple morbilliform rash, without systemic involvement; 22 had a complex morbilliform rash with systemic involvement, including 9 with cutaneous manifestations of graft versus host disease (GVHD) and 13 with rashes secondary to drug exposure.

The majority of the patients had a hematologic malignancy (18 with a simple rash, and 16 with a complex rash); the rest had a solid organ malignancy (9 with a simple rash and 6 with a complex rash).

Nearly one-third (30.6%) of patients died within 6 months of having a dermatologic consultation. These patients showed significantly higher levels of serum elafin – a protein that is not detectable in normal skin but is overexpressed in wound healing and inflammatory disorders – as well as IL-6 and TNF-alpha, compared with patients who were alive at 6 months.

“While GVHD and drug-related SCARs are difficult to distinguish clinically, our results suggest that elafin may be a useful biomarker to identify patients with a suspected diagnosis of SCARs or GVHD who are at increased risk of death within 6 months,” the investigators wrote. “Given its broad anti-inflammatory activity, elafin’s potential as a therapeutic agent for SCARs should be further explored.”

They noted that elevated TNF-alpha levels pointed to another potential therapeutic target for SCARs among patients undergoing treatment for cancer. Patients who died were also less likely to have elevated bilirubin level relative to baseline than patients who survived past 6 months.

The patients with a complex morbilliform rash caused by drug exposure had significantly higher median levels of IL-10 and IL-6, compared with those with a complex rash related to GVHD or with a simple rash. “Thought to originate from activated keratinocytes in TEN [toxic epidermal necrolysis], elevated IL-10 may reflect a defense mechanism against drug-specific cytotoxic T cells that are activated during the disease process,” the authors wrote.

Patients with complex rash also had a significantly higher median white blood cell count and higher median values for all cytokines, compared with the simple rash group, although only differences in TNF-alpha levels were statistically significant.

“A larger, prospective study examining the association of cytokines with SCARs is needed, as well as longitudinal assessment of cytokine levels to assess their prognostic significance,” the authors wrote. “This exploratory analysis presents potential therapeutic targets in a high-risk patient population, for whom a ‘complex’ rash can disrupt and delay treatment of underlying disease.”

The study was partly funded by the National Cancer Institute/National Institutes of Health via a grant to the Memorial Sloan Kettering Cancer Center. One author declared support from a Dermatology Foundation Career Development Award.

SOURCE: Mori S et al. J Am Acad Dermatol, 2018 October 26. doi: 10.1016/j.jaad.2018.10.039.

Researchers have identified biomarkers that might eventually be used to flag cancer patients with severe cutaneous adverse reactions (SCARs) at an increased risk of mortality.

In a retrospective study, elevated elafin, interleukin (IL)-6, and tumor necrosis factor (TNF)–alpha levels were significantly associated with a greater risk of all-cause mortality among hospitalized cancer patients who developed SCARs, which includes Stevens-Johnson syndrome, toxic epidermal necrolysis, and drug-induced hypersensitivity syndrome.

In the study, published in the Journal of the American Academy of Dermatology, Shoko Mori of the dermatology service at Memorial Sloan Kettering Cancer Center, New York, and coauthors looked at 49 cancer patients hospitalized (41) or treated at an urgent care center (8), between August 2016 and July 2017 who experienced a morbilliform rash. Overall, 27 patients had a simple morbilliform rash, without systemic involvement; 22 had a complex morbilliform rash with systemic involvement, including 9 with cutaneous manifestations of graft versus host disease (GVHD) and 13 with rashes secondary to drug exposure.

The majority of the patients had a hematologic malignancy (18 with a simple rash, and 16 with a complex rash); the rest had a solid organ malignancy (9 with a simple rash and 6 with a complex rash).

Nearly one-third (30.6%) of patients died within 6 months of having a dermatologic consultation. These patients showed significantly higher levels of serum elafin – a protein that is not detectable in normal skin but is overexpressed in wound healing and inflammatory disorders – as well as IL-6 and TNF-alpha, compared with patients who were alive at 6 months.

“While GVHD and drug-related SCARs are difficult to distinguish clinically, our results suggest that elafin may be a useful biomarker to identify patients with a suspected diagnosis of SCARs or GVHD who are at increased risk of death within 6 months,” the investigators wrote. “Given its broad anti-inflammatory activity, elafin’s potential as a therapeutic agent for SCARs should be further explored.”

They noted that elevated TNF-alpha levels pointed to another potential therapeutic target for SCARs among patients undergoing treatment for cancer. Patients who died were also less likely to have elevated bilirubin level relative to baseline than patients who survived past 6 months.

The patients with a complex morbilliform rash caused by drug exposure had significantly higher median levels of IL-10 and IL-6, compared with those with a complex rash related to GVHD or with a simple rash. “Thought to originate from activated keratinocytes in TEN [toxic epidermal necrolysis], elevated IL-10 may reflect a defense mechanism against drug-specific cytotoxic T cells that are activated during the disease process,” the authors wrote.

Patients with complex rash also had a significantly higher median white blood cell count and higher median values for all cytokines, compared with the simple rash group, although only differences in TNF-alpha levels were statistically significant.

“A larger, prospective study examining the association of cytokines with SCARs is needed, as well as longitudinal assessment of cytokine levels to assess their prognostic significance,” the authors wrote. “This exploratory analysis presents potential therapeutic targets in a high-risk patient population, for whom a ‘complex’ rash can disrupt and delay treatment of underlying disease.”

The study was partly funded by the National Cancer Institute/National Institutes of Health via a grant to the Memorial Sloan Kettering Cancer Center. One author declared support from a Dermatology Foundation Career Development Award.

SOURCE: Mori S et al. J Am Acad Dermatol, 2018 October 26. doi: 10.1016/j.jaad.2018.10.039.