Mutations in the ribosome biogenesis factor gene LTV1 are linked to LIPHAK syndrome, a novel poikiloderma-like disorder.

In the framework of the UK 100 000 Genomes Project, we investigated the genetic origin of a previously undescribed recessive dermatological condition, which we named LIPHAK (LTV1-associated Inflammatory Poikiloderma with Hair abnormalities and Acral Keratoses), in four affected individuals from two UK families of Pakistani and Indian origins, respectively. Our analysis showed that only one gene, LTV1, carried rare biallelic variants that were shared in all affected individuals, and specifically they bore the NM_032860.5:c.503A > G, p.(Asn168Ser) change, found homozygously in all of them. In addition, high-resolution homozygosity mapping revealed the presence of a small 652-kb stretch on chromosome 6, encompassing LTV1, that was haploidentical and common to all affected individuals. The c.503A > G variant was predicted by in silico tools to affect the correct splicing of LTV1's exon 5. Minigene-driven splicing assays in HEK293T cells and in a skin sample from one of the patients confirmed that this variant was indeed responsible for the creation of a new donor splice site, resulting in aberrant splicing and in a premature termination codon in exon 6 of this gene. LTV1 encodes one of the ribosome biogenesis factors that promote the assembly of the small (40S) ribosomal subunit. In yeast, defects in LTV1 alter the export of nascent ribosomal subunits to the cytoplasm; however, the role of this gene in human pathology is unknown to date. Our data suggest that LIPHAK could be a previously unrecognized ribosomopathy.

Tap water iontophoresis in the treatment of pediatric hyperhidrosis.

AIM OF THE STUDY: The treatment options for localized hyperhidrosis include antiperspirants, anticholinergics, iontophoresis, botulinum toxin and surgery. Tap water iontophoresis (TWI) involves immersing the affected area in tap water and passing a small electrical current through the area. Our aim was to assess the success of this therapy in a pediatric cohort. METHODS: Retrospective case note review of all patients younger than 18years who underwent TWI between 2002 and 2015. Demographic data, number of treatment sessions, side effects and overall success were analyzed. Individuals undergo 7 treatments over 4weeks. A positive outcome was determined as an improvement in symptoms. Pre- and posttreatment hyperhidrosis disease severity scale (HDSS) was measured. Data are presented as mean (range). Statistical analysis was by paired t-test. A P value of <0.05 was regarded as significant. RESULTS: There were 43 patients (30 females) with a mean age of 15 (8-17) years. Palmar and/or plantar hyperhidrosis (PPH) was present in 39/43 (91%) patients. Axillary hyperhidrosis (AH) was present in 19/43 (44%) patients. All patients (with the exception of one) underwent 7 sessions (5-7). Side effects included paresthesia (88%), pruritus (26%), pain (26%), erythema (14%), dryness (12%) as well as vesicle formation and abrasions in one patient (2%). A positive outcome was found in 84% (36/43) of patients. There was a significant reduction in mean HDSS (pre 3.5 vs. post 2; P=0.0001). CONCLUSION: TWI is a safe and effective modality of treatment for both PPH and AH in the pediatric population, with minimal side effects. Pediatric surgeons should offer this treatment option before considering more invasive surgical procedures. LEVEL OF EVIDENCE: IV: Retrospective study.

Reliability of dermoscopy in the assessment of patients with Raynaud's phenomenon.

OBJECTIVE: Few rheumatologists have access to wide field or video capillaroscopy (abnormal capillaries being highly predictive of CTD), and a key question is whether they should, therefore, purchase a dermatoscope. The aim of this study was to estimate the inter- and intra-observer variability of dermoscopy (magnification 10x) among rheumatologists with little or no experience of the technique. Good reliability is a necessary prerequisite for a test to be a valid clinical or research tool. METHODS: Dermoscopy was performed in all 10 nail folds from 16 subjects with a range of capillary normality/abnormality. The 160 nail fold images thus acquired were made into two PowerPoint presentations, each of 80 images with 16 duplicate slides. Each participating rheumatologist graded one of the sets of 96 images, grading scale (0-3): normal, mildly abnormal/'suspicious', definitely abnormal, grossly abnormal capillaries or 'unclassifiable' when capillaries could not be adequately identified. Data from both presentations were pooled for analysis. RESULTS: Twenty-eight rheumatologists participated in the study. For the decision as to whether an image could be classified or not, the inter- and intra-observer kappa-coefficients were 0.59 (95% CI 0.51, 0.67) and 0.63 (95% CI 0.45, 0.74), respectively. Conditional on being able to classify, the intra-class correlation coefficient for inter- and intra-observer reliability was 0.72 (95% CI 0.66, 0.77) and 0.85 (95% CI 0.82, 0.92), respectively. CONCLUSIONS: Inter- and intra-observer reliability were good, suggesting that with little training, dermoscopy is likely to be a useful technique to identify capillary distortions/underlying CTD.