Case Report: ISG15 deficiency caused by novel variants in two families and effective treatment with Janus kinase inhibition.

ISG15 deficiency is a rare disease caused by autosomal recessive variants in the ISG15 gene, which encodes the ISG15 protein. The ISG15 protein plays a dual role in both the type I and II interferon (IFN) immune pathways. Extracellularly, the ISG15 protein is essential for IFN-γ-dependent anti-mycobacterial immunity, while intracellularly, ISG15 is necessary for USP18-mediated downregulation of IFN-α/ß signalling. Due to this dual role, ISG15 deficiency can present with various clinical phenotypes, ranging from susceptibility to mycobacterial infection to autoinflammation characterised by necrotising skin lesions, intracerebral calcification, and pulmonary involvement. In this report, we describe novel variants found in two different families that result in complete ISG15 deficiency and severe skin ulceration. Whole exome sequencing identified a heterozygous missense p.Q16X ISG15 variant and a heterozygous multigene 1p36.33 deletion in the proband from the first family. In the second family, a homozygous total ISG15 gene deletion was detected in two siblings. We also conducted further analysis, including characterisation of cytokine dysregulation, interferon-stimulated gene expression, and p-STAT1 activation in lymphocytes and lesional tissue. Finally, we demonstrate the complete and rapid resolution of clinical symptoms associated with ISG15 deficiency in one sibling from the second family following treatment with the Janus kinase (JAK) inhibitor baricitinib.

Oxygen saturation thresholds in bronchiolitis: examining admissions.

OBJECTIVE: Examine admissions for bronchiolitis, comparing centres with oxygen saturation thresholds for admission of 90% versus 92%. DESIGN: Prospective multi-centre service evaluation, all admissions for bronchiolitis during 4-week period, November 2018. SETTING: Paediatric departments across 12 hospitals in the West Midlands, UK. PATIENTS: 320 patients aged 6 weeks-1 year, diagnosis of bronchiolitis, exclusions: chronic illness or high dependency/intensive care admission. MAIN OUTCOME MEASURES: Reason for admission, admission saturations and length of stay. RESULTS: Inadequate feeding was the the most common reason for admission (80%). Only 20 patients were admitted solely because of low saturations. Median peripheral oxygen saturation in this group was 88%. Median length of stay in 90% centres was 41 hours, against 59 hours for 92% centres (p=0.0074). CONCLUSIONS: Few patients were admitted solely due to low oxygen saturations, only one had a potentially avoidable admission if thresholds were 90%. Length of stay was significantly reduced in the 90% threshold centres.

Fifteen-minute consultation: How to use an interpreter in a medical consultation.

The use of interpreters is essential in our multicultural society. The families and patients we treat come from differing backgrounds, cultures and spoken language. Many are not proficient in, or may even entirely lack, the ability to communicate effectively in English. As health professionals, we must meet their needs and manage the risks to provision of good quality care that language barriers may introduce. Use of an interpreter or interpreting service is an important skill, which is rarely formally taught in undergraduate or postgraduate curricula. Here, we present some of the pitfalls of using an interpreter, and offer some tips on getting the best out of their use.

Fifteen-minute consultation: Asking questions: the puzzles and problems model.

People are full of useful advice, especially when you make the transition to the senior doctor grade. We present a very helpful model we have used over some time to aid us when we have issues.