Low-dose oral isotretinoin in the treatment of recalcitrant facial flat warts: A clinical case and review of literature.

Background and Aims: The treatment of recalcitrant facial flat warts has always been challenging for dermatologists. The pain related to the application of the different treatments, side effects and costs are determining factors in the choice of therapy. To date, it is known that oral isotretinoin administered at a dose of 0.5 mg/kg/day is effective and safe; However, the different adverse effects reported have a dose-dependent behavior and they could limit their use. Our aim is to assess the effect of low-doses of oral isotretinoin to reducing side effects in the complete removal of recalcitrant facial flat warts and the current evidence in this regard. Methods: An extensive literature review was conducted to identify articles relating to low doses of oral isotretinoin for recalcitrant flat warts treatment, regardless of design up to May 2023. Results: The literature search yielded eight articles of 324 reviewed meeting criteria. Isotretinoin was administered in doses of 0.1-0.5 mg/kg/day. Complete elimination of the lesions occurred in 65.13% of the patients and a partial response in 19.26%. Four relapses were documented at the 4-month follow-up. The most frequent adverse effect was cheilitis. Conclusion: We might consider low doses of oral isotretinoin for the treatment of recalcitrant facial flat warts in which side effects need to be reduced. However, current published works have several limitations, including small sample sizes, lack of control group and follow-up periods. Larger, randomized, controlled studies are needed to verify the efficacy and safety of different doses of isotretinoin.

Potential Role of Protein Kinase FAM20C on the Brain in Raine Syndrome, an In Silico Analysis.

FAM20C (family with sequence similarity 20, member C) is a serine/threonine-specific protein kinase that is ubiquitously expressed and mainly associated with biomineralization and phosphatemia regulation. It is mostly known due to pathogenic variants causing its deficiency, which results in Raine syndrome (RNS), a sclerosing bone dysplasia with hypophosphatemia. The phenotype is recognized by the skeletal features, which are related to hypophosphorylation of different FAM20C bone-target proteins. However, FAM20C has many targets, including brain proteins and the cerebrospinal fluid phosphoproteome. Individuals with RNS can have developmental delay, intellectual disability, seizures, and structural brain defects, but little is known about FAM20C brain-target-protein dysregulation or about a potential pathogenesis associated with neurologic features. In order to identify the potential FAM20C actions on the brain, an in silico analysis was conducted. Structural and functional defects reported in RNS were described; FAM20C targets and interactors were identified, including their brain expression. Gene ontology of molecular processes, function, and components was completed for these targets, as well as for potential involved signaling pathways and diseases. The BioGRID and Human Protein Atlas databases, the Gorilla tool, and the PANTHER and DisGeNET databases were used. Results show that genes with high expression in the brain are involved in cholesterol and lipoprotein processes, plus axo-dendritic transport and the neuron part. These results could highlight some proteins involved in the neurologic pathogenesis of RNS.

FAM20C Overview: Classic and Novel Targets, Pathogenic Variants and Raine Syndrome Phenotypes.

FAM20C is a gene coding for a protein kinase that targets S-X-E/pS motifs on different phosphoproteins belonging to diverse tissues. Pathogenic variants of FAM20C are responsible for Raine syndrome (RS), initially described as a lethal and congenital osteosclerotic dysplasia characterized by generalized atherosclerosis with periosteal bone formation, characteristic facial dysmorphisms and intracerebral calcifications. The aim of this review is to give an overview of targets and variants of FAM20C as well as RS aspects. We performed a wide phenotypic review focusing on clinical aspects and differences between all lethal (LRS) and non-lethal (NLRS) reported cases, besides the FAM20C pathogenic variant description for each. As new targets of FAM20C kinase have been identified, we reviewed FAM20C targets and their functions in bone and other tissues, with emphasis on novel targets not previously considered. We found the classic lethal and milder non-lethal phenotypes. The milder phenotype is defined by a large spectrum ranging from osteonecrosis to osteosclerosis with additional congenital defects or intellectual disability in some cases. We discuss our current understanding of FAM20C deficiency, its mechanism in RS through classic FAM20C targets in bone tissue and its potential biological relevance through novel targets in non-bone tissues.

Systematic Review of Clinimetric Instruments to determine the severity of Non-segmental Vitiligo.

This systematic review of measurement instruments for vitiligo outcomes included validation articles published from 2011 to May 2018. According to the PRISMA statement, the search was carried out in EMBASE (via OvidSP); MEDLINE (via OvidSP and PubMed). The COSMIN taxonomy will be used to define the measurement properties. Inclusion criteria were original studies reporting measuring properties. Exclusion criteria were clinical trials using scales whose measurement properties were not assessed, studies of cross-cultural adaptation, scales focused on other aspects of the disease such as quality of life, satisfaction, disease's burden. Fourteen studies were identified, which described 15 instruments to measure vitiligo outcomes. Nine of them, measured properties related to the severity of the disease: Vitiligo extent score (VES), Self-Assessment Vitiligo Extent Score (SA-VES), Self-Assessed Vitiligo Area Scoring Index (SAVASI), Vitiligo Area Scoring Index (VASI), Vitiligo European Task Force assessment (VETFa), Vitíligo Noticeability Scale (VNS), Koebner's phenomenon in vitiligo score (K-VSCOR), Vitiligo Extent Tensity Index (VETI), Potential Repigmentation Index (PRI). The most effective tool to asses affected Body Surface Area (BSA) is VES. The VASI is useful to stratify by severity. There is not enough evidence to recommend the use of SAVASI. The VETFa does not offer any difference to calculate the affected BSA compared with the rule of 9's. The VNS and K-VSCOR lack of reliability evidence.

A double-blind, randomized, placebo-controlled trial of oral isotretinoin in the treatment of recalcitrant facial flat warts.

UNLABELLED: Abstract Background: Recalcitrant facial flat warts are caused by human papillomavirus and may persist for years despite treatment. Isotretinoin has demonstrated benefits in the treatment of recalcitrant, genital and common warts, but placebo-controlled trials have not been performed. OBJECTIVE: To determine whether isotretinoin is safe and effective for recalcitrant facial flat warts. METHODS: Isotretinoin 30 mg/day or placebo was administered to 16 and 15 patients, respectively, in double-blind, randomized fashion for 12 weeks. Cutaneous lesions were assessed and adverse events including serologic and ophthalmologic changes were recorded. It is considered that warts were recalcitrant if the patient was treated for at least 3 years with at least three of the following options: retinoids, 5-fluorouracil, imiquimod and cryotherapy using liquid nitrogen. RESULTS: Each patient in the istotretinoin group showed complete clearance of all flat warts, while none of the patients in the placebo group showed any improvement (p=0.0001). The most frequent adverse event was cheilitis. There were no statistically significant changes in the laboratory findings. LIMITATIONS: The study design does not permit complete blinding of the dermatologist who can easily recognize the adverse effects of isotretinoin. The clinical findings, however, were so dramatic that this would not have impacted the findings. Another limitation of the study is a lack of follow-up to assess for recurrence after the drug was discontinued. CONCLUSIONS: Isotretinoin is an effective treatment for recalcitrant flat facial warts with a well-known, manageable safety profile.