Tofacitinib ameliorates skin inflammation in a case of severe autosomal recessive congenital ichthyosis.
Yu-Chen LinYi-Kai HongWilson Jr F AalaKiyotaka HitomiMasashi AkiyamaJohn A McGrathChao-Kai HsuPublished in: Clinical and experimental dermatology (2024)
Autosomal recessive congenital ichthyosis (ARCI) is a genetically heterogeneous disorder manifesting aberrant skin scaling and increased transepidermal water loss (TEWL). Current treatments for ARCI are limited and sub-optimal. We studied a 27-year-old man with ARCI resulting from a homozygous missense variant in TGM1 (transglutaminase 1). RNA-sequencing of lesional skin revealed aberrant JAK-STAT signalling, providing a rationale for innovative treatment with a Janus kinase inhibitor. We prescribed oral tofacitinib (11 mg daily) for 26 weeks. Rapid improvements in erythema and fissuring manifested within the first month. Sustained reductions in 5-D itch scale and Dermatology Life Quality Index (DLQI) scores were also observed. TEWL decreased for the first 10 weeks but increased thereafter. Tofacitinib down-regulated inflammatory genes and pathways, while enhancing skin barrier markers. Moreover, TGM1 distribution was normalized although enzymatic activity remained deficient. This study suggests that oral tofacitinib may be a useful therapy to consider in patients with ARCI.
Keyphrases
- rheumatoid arthritis
- soft tissue
- wound healing
- ulcerative colitis
- intellectual disability
- oxidative stress
- single cell
- clinical trial
- physical activity
- transcription factor
- stem cells
- hydrogen peroxide
- early onset
- genome wide
- muscular dystrophy
- nitric oxide
- gene expression
- bone marrow
- autism spectrum disorder
- mesenchymal stem cells
- preterm birth
- solid state