The association of hypophosphataemic rickets with verrucous epidermal naevus (EN) and elevated fibroblast growth factor 23 levels is known as cutaneous-skeletal hypophosphataemia syndrome (CSHS), and can be caused by somatic activating mutations in RAS genes. We report a unique patient with CSHS associated with giant congenital melanocytic naevus (CMN), neurocutaneous melanosis and EN syndrome, manifesting as facial linear sebaceous naevus, developmental delay and ocular dermoids. An activating mutation Q61R in the NRAS gene was found in affected skin and ocular tissue but not blood, implying that the disparate manifestations are due to a multilineage activating mutation (mosaic RASopathy). We speculate on the apparently rare association of CSHS with CMN compared with EN. We also report the favourable outcome of this patient at the age of 8 years after extensive neonatal curettage of the giant CMN and use of vitamin D and phosphate supplementation.
Background
Narrowband ultraviolet B phototherapy (nbUVB) is a well‐established, well‐tolerated and efficacious treatment for eczema. There is a distinct lack of literature surrounding the therapeutic use of nbUVB in eczema in children and especially in children with higher skin phototypes (III to VI).
Methods
We undertook a retrospective review of children aged 18 years and under with eczema who had undergone nbUVB in our department between 1 January 2011 and 31 December 2017. Abstracted data included sex, age, skin phototype, severity as graded by a paediatric dermatologist, cumulative dose, response to treatment and subsequent remission.
Results
In total, 60 children had nbUVB. Of those, 56 had more than 10 nbUVB exposures. Complete or near‐complete clearance was achieved in 31 children (52%). Of those, 24 (77%) had a skin phototype of III or greater. Clinical remission rates of these patients were 100%, 87%, 57% and 52% at 0, 3, 6 and 12 months, respectively. Seventeen patients (28%) suffered side effects. Most commonly these were mild side effects such as erythema and xerosis.
Conclusion
We have demonstrated that nbUVB is a safe, well‐tolerated and efficacious form of treatment for children with atopic eczema. We have shown it to be effective in those with skin phototypes greater than III and shown that they are a group that may derive greater long‐term efficacy. In clinical practice, preference for nbUVB as second‐line treatment, over oral systemics, should always be considered.
Targeted biologic therapies can elicit an undesirable host immune response characterized by the development of antidrug antibodies (ADA), an important cause of treatment failure. The most widely used biologic across immune-mediated diseases is adalimumab, a tumor necrosis factor inhibitor. This study aimed to identify genetic variants that contribute to the development of ADA against adalimumab, thereby influencing treatment failure. In patients with psoriasis on their first course of adalimumab, in whom serum ADA had been evaluated 6–36 months after starting treatment, we observed a genome-wide association with ADA against adalimumab within the major histocompatibility complex (MHC). The association signal mapped to the presence of tryptophan at position 9 and lysine at position 71 of the HLA-DR peptide-binding groove, with both residues conferring protection against ADA. Underscoring their clinical relevance, these residues were also protective against treatment failure. Our findings highlight antigenic peptide presentation via MHC class II as a critical mechanism in the development of ADA against biologic therapies and downstream treatment response.
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