Secukinumab use in the treatment of Netherton's syndrome

Gan, Christian; King, E. S. J.; Orchard, David

doi:10.1111/ajd.13880

Cited by 10 publications

(10 citation statements)

References 4 publications

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“…Candidial onychomycosis developed in two additional patients 15 . In additional two reports, secukinumab led to remarkable and sustained clinical improvement in a total three NS cases 24,25 …”

Section: Discussionmentioning

confidence: 90%

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Ustekinumab therapy for Netherton syndrome

Samuelov

Shehadeh

Sarig

et al. 2022

The Journal of Dermatology

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Netherton syndrome (NS) is a rare disorder of cornification associated with high morbidity. It is caused by bi‐allelic mutations in SPINK5 encoding the serine protease inhibitor LEKTI. Previous studies have shown Th17 skewing with IL‐23 upregulation in NS, raising the possibility that targeting these inflammatory pathways may alleviate disease manifestations. We ascertained the therapeutic efficacy of six doses of ustekinumab administered to three patients with NS over a period of 13 months using the Ichthyosis Area and Severity Index (IASI), the Dermatology Life Quality Index (DLQI), a visual analogue scale (VAS) for itch and the peak‐pruritus numeric rating scale (PP‐NRS). Histopathology analysis including CD3, CD4, CD8 and interleukin 17 (IL‐17) immunostaining, was performed at baseline and 4 weeks following the last ustekinumab dose. Total IASI scores were reduced by 28% in two patients at week 16 with sustained response by week 56. No consistent improvement in DLQI, VAS for itch and PP‐NRS scores was observed. The inflammatory infiltrate and the degree of acanthosis were slightly reduced at week 56 as compared to baseline. No significant change in immunostaining of the various inflammatory markers was observed at week 56. In conclusion, this case series did not demonstrate a significant therapeutic effect of ustekinumab in NS.

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Section: Discussionmentioning

confidence: 90%

“…15 In additional two reports, secukinumab led to remarkable and sustained clinical improvement in a total three NS cases. 24,25 Besides IL-12/23 and IL-17 blockade, other targeted biologic therapies have been investigated for clinical efficacy in NS. TNFalpha blockade with infliximab resulted in both cutaneous and hair improvement.…”

Section: Con Clus Ionsmentioning

confidence: 99%

Ustekinumab therapy for Netherton syndrome

Samuelov

Shehadeh

Sarig

et al. 2022

The Journal of Dermatology

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“…1,4 An IL-17 immune profile was recently suggested in NS, and significant improvement was achieved with secukinumab. 10 An exacerbation of pruritus was reported in a patient together with the worsening of ILC lesions. 4 In our patient, however, the ILC lesions were not pruritic, even in their most widespread form, after dupilumab eliminated his atopic signs and symptoms.…”

Section: Discussionmentioning

confidence: 94%

Long‐term dupilumab therapy in Netherton syndrome with severe atopic manifestations: Case report and review of the literature

et al. 2023

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We herein present a unique patient of Netherton syndrome (NS) with ichthyosis linearis circumflexa (ILC) lesions associated with severe atopic manifestations since infancy, showing different responses of atopic and ILC lesions to a 2‐year dupilumab therapy. The atopic eczematous lesions and pruritus healed remarkably, dramatically improving the patient's quality of life, whilst the scalp hair showed a clinical and light microscopic improvement. The additional recovery in axillary/pubic/extremity hair growth, sweating and nail growth in the presented case was not previously reported in NS patients treated with dupilumab. However, dupilumab had no therapeutic effect on ILC lesions which were not pruritic and showed a treatment‐independent wax and waned course.

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“…Our data corroborates the heightened Th17 inflammatory response seen previously in CI patients [19–21], which has stimulated investigations of the IL-17A inhibitor secukinumab as therapy for CI. While there are sporadic case reports of secukinumab improving a patient with autosomal recessive congenital ichthyosis harboring an ABCA12 variant [35], as well as patients with Netherton’s syndrome [36, 37], a double-blind randomized controlled trial evaluating secukinumab in 4 types of CI patients compared to placebo failed to reduce disease severity or reduce Th17-related biomarkers [38]. Consistent with one study from 2019 [20], our data shows all CI dysbiosis clusters with elevated IL-17A and IL-17F.…”

Section: Discussionmentioning

confidence: 99%

Altered skin microbiome, inflammation, and JAK/STAT signaling in Southeast Asian ichthyosis patients

Huynh

Hoang

et al. 2022

Preprint

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Cutaneous ichthyosis (CI) is a collective group of monogenetic disorders of cornification demonstrating epidermal scaling, fissuring, chronic skin inflammation, and increased susceptibility to infection. In healthy individuals the skin microbiome limits growth of pathogenic organisms; however, the microbiome signature in CI is poorly characterized. To rectify this, we investigated the microbiome signature across 7 subtypes of CI in 43 individuals of Southeast Asian ethnicity, of which exome sequencing revealed 20 novel and 31 recurrent pathogenic variants. Microbiome meta-analysis revealed distinct microbial populations, reduced commensal microbiota, and higher colonization by pathogenic species. This correlated with increased production of inflammatory cytokines, including Th17 and JAK/STAT signaling, in peripheral blood mononuclear cells. Moreover, we identified microbiota and inflammation alterations in wounds of CI patients responsible for impaired wound healing. Together, this research enhances our understanding of the microbiological, immunological, and molecular properties of CI patients and provides critical information for improving therapeutic management.

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Secukinumab use in the treatment of Netherton's syndrome

Abstract: Netherton syndrome is a rare, severe genetic disorder of cornification without specific treatment. We describe two cases who demonstrated marked cutaneous improvement with secukinumab and suggest a role for IL-17 therapy in treating this condition.

Cited by 10 publications

References 4 publications

Ustekinumab therapy for Netherton syndrome

Ustekinumab therapy for Netherton syndrome

Long‐term dupilumab therapy in Netherton syndrome with severe atopic manifestations: Case report and review of the literature

Altered skin microbiome, inflammation, and JAK/STAT signaling in Southeast Asian ichthyosis patients

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