Successful treatment of Netherton syndrome with ustekinumab in a 15‐year‐old girl

Abstract

Our results suggest that IRF4 rs12203592 is associated with poorer melanoma-specific survival, largely mediated through Breslow thickness, reinforcing our previous findings related to rs12203592*T and tumour thickness. 1 This variant's adverse effect on survival may occur through its functional effect on IRF4 expression. The SNP is known to modulate IRF4 enhancer-mediated transcriptional regulation in melanocytes, and it may play a similar role in immune cells. 6 Increased IRF4 expression in immune cells and the subsequent activation of the TERT promoter has been shown to increase telomerase activity, which in turn has been associated with increased Breslow thickness and tumour progression. 7,8 In lymphocytes, rs12203592*T results in higher IRF4 expression, and it has been suggested that this may enable suppressive regulatory T cells to inhibit the immune response, enabling an acceleration in tumour growth and progression. 2 In conclusion, IRF4 rs12203592 appears to play a role in melanoma prognosis, which is seemingly mediated by the SNP's association with Breslow thickness at diagnosis. The effect on survival does not appear to be site specific. Further studies are now required to confirm the pathway and mechanism by which this SNP affects survival, and to determine the potential clinical and prognostic utility of these findings.

Successful treatment with dupilumab of an adult with Netherton syndrome

“…One study including three patients with NS observed increased Th1 marker levels in patients with NS similar to that of patients with AD and patients with psoriasis 2 . A recent case report demonstrated a clinical effect of treatment with ustekinumab, which is an IL‐12/‐23 antibody, in a 15‐year‐old girl with NS 8 . Importantly, anti‐inflammatory treatment cannot treat the primary skin barrier defect, and patients with NS need to continue applying emollients daily.…”

Netherton Syndrome in Children: Management and Future Perspectives

“…While IL-17 was found to be a dominant immune profile in NS, the authors took into consideration influencing the IL-17/IL-23 axis as an effective interventional approach. Therefore, therapy with an IL-17 inhibitor might be another possible strategy of treatment for patients with NS ( 54 ).…”

Netherton syndrome caused by compound heterozygous mutation, c.80A>G mutation in SPINK5 and large‐sized genomic deletion mutation, and successful treatment of intravenous immunoglobulin

“…The lesser epidermal permeation in comparison with tacrolimus may offer an added advantage in patients with NS (Oji et al, 2005; Saif & Al‐Khenaizan, 2007). Biologics targeting IL4/IL13 (Dupilumab) (Steuer & Cohen, 2020), IL23 (Ustekinumab) (Volc et al, 2020), IL17 (Secukinuma, Ixekimab) (Claire et al, 2020; Luchsinger et al, 2020), and TNF‐α (Infliximab) (Fontao et al, 2020) have been reported as effective in some patients with NS. Treatment with IVIG was beneficial in seven patients with NS to date, although its immunomodulatory mechanisms are not understood (Renner et al, 2009; Small & Cordoro, 2016).…”