Date: 06/25/2020

Medical Scientific Advisory Board (MSAB) of the Foundation for Ichthyosis and Related Skin Types

FIRST Quarterly Literature Review

Edited by Emily Henkel, MD, MPH

Dell Medical School, Austin, TX

Title: Secukinumab Therapy for Netherton Syndrome

Journal: JAMA Dermatology

Publication Type & Date: Case Series; May 2020
Reference: Luchsinger, Isabelle, et al. "Secukinumab Therapy for Netherton Syndrome." JAMA Dermatology.   PMID: 32459284    DOI: 10.1001/jamadermatol.2020.1019

Review: Previous research has demonstrated increased activity of the helper T cell 17/interleukin 23 pathway in patients with Netherton Syndrome. When activated, these cells release IL-17, which stimulates skin cells (keratinocytes) to proliferate. A medication commonly used for psoriasis, secukinumab (Cosentyx®) is designed to stop this signal. This case series evaluated the efficacy of using secukinumab to treat four patients with Netherton Syndrome. Significant improvement in ichthyosis area, severity, itch, and quality of life was seen in all patients by three months and was measured using established scales (Ichthyosis area and severity index, 5-D itch scale). The best results were seen in the two pediatric patients with the erythrodermic subtype. Three patients were followed for 6-12 months and all chose to remain on the medication. The only side effects experienced during this time were nail fungus infection and an itchy eczema reaction on the palms. This research shows promise that this medication may be beneficial to Netherton Syndrome patients with severe erythema and itch and should be investigated further with more patients over a long period of time.

Summary; For patients with Netherton Syndrome and severe itch and diffuse redness (erythroderma), a treatment option can be considered, as noted, in the summary above.

Title: Ichthyosis affects mental health in adults and children: A cross-sectional study

Journal: JAAD

Publication Type & Date: Research Letter (in press); Jan 2020

Reference: Sun, Qisi, et al. "Ichthyosis affects mental health in adults and children: A cross-sectional study." Journal of the American Academy of Dermatology (2020).
PMID: 32006604 DOI: 10.1016/j.jaad.2020.01.052

Review: Patients with ichthyosis face daily challenges that may include discomfort, harassment, and difficulty engaging in work or leisure activities as a result of their disorder. This study surveyed 181 patients from the National Ichthyosis Registry to investigate the psychiatric impact of the disorder. The patients were surveyed using questionnaires (PHQ-9, GAD-7) commonly utilized to screen for anxiety, depression and quality of life in patients with other medical conditions. The results showed that among adults with ichthyosis, 34% screened positive for depression, 27% positive for anxiety, and 95% experienced impairment in their quality of life. The results were similar in the pediatric population with 30% positive for depression, 38% positive for anxiety, and 85% with quality of life impairment. Most participants surveyed had the autosomal recessive congenital ichthyosis (ARCI) subtype and the results did not differ significantly between those with severe versus those with moderate disease severity. These data highlight the need for physicians to screen ichthyosis patients in order to detect any psychologic sequelae and provide appropriate care.

Summary; As known by many patients and families impacted by any type of ichthyosis, the potential impact on personal interactions and behavioral differences cannot be overlooked.  While formal screening for, for instance, depression (as done in this study) can be considered, from a practical stance, such information should be sought from patients and/or family members when evaluating our patients.

Title: Association of the Severity of Alopecia with the Severity of Ichthyosis

Journal: JAMA Dermatology

Publication Type & Date: Research Letter; Sept 2019

Reference: Putterman, Elana, et al. "Association of the Severity of Alopecia With the Severity of Ichthyosis." JAMA dermatology 155.9 (2019): 1077-1078.

PMID: 31365037 DOI: 10.1001/jamadermatol.2019.1520

Review: Hair loss (alopecia) is commonly reported in patients with ichthyosis, but not much is known about why this happens or if it is associated with a particular subtype or severity of ichthyosis. This small study was conducted with 86 patients from the National Registry for Ichthyosis and Related Skin Types to investigate if hair loss can be predicted based on disease severity or the genetics related to subtypes. In this study, two experts examined photographs of each patient without knowing their genetic subtype and scored the severity of hair loss and skin findings. The results showed that there was no significant relationship between the severity of skin findings and hair loss severity. However, when they separated the patients by genetic subtype, those with TGM1 and ABCA12 mutations appeared to have more severe hair loss in association with their greater skin disease severity. While previous research has shown the association of hair loss with TGM1 mutation, these results suggest that ABCA12 mutation may also be associated with hair loss in milder phenotypes in addition to the known association of severe hair loss in those with harlequin ichthyosis. Additionally, patients in these subtypes may suffer from more severe hair loss if they have severe skin symptoms than patients in these subtypes with more moderate skin findings.

Summary; While ichthyosis can, in some cases, be associated with hair loss or alopecia, there does seem to be relationship with more severe types of disease as noted by most physicians caring for these patients and by the patients, themselves.  The authors seem to confirm the relationship with certain genetic mutations which can be associated with more severe disease, overall, as well as in some of the milder clinical subtypes.