Summary
Cutaneous skeletal hypophosphatemia syndrome (CSHS), caused by somatic
RAS
mutations, features excess fibroblast growth factor-23 (FGF23) and skeletal dysplasia. Records from 56 individuals ...were reviewed and demonstrated fractures, scoliosis, and non-congenital hypophosphatemia that in some cases were resolved. Phosphate and calcitriol, but not skin lesion removal, were effective at controlling hypophosphatemia. No skeletal malignancies were found.
Purpose
CSHS is a disorder defined by the association of epidermal and/or melanocytic nevi, a mosaic skeletal dysplasia, and an FGF23-mediated hypophosphatemia. To date, somatic
RAS
mutations have been identified in all patients whose affected tissue has undergone DNA sequencing. However, the clinical spectrum and treatment are poorly defined in CSHS. The purpose of this study is to determine the spectrum of the phenotype, natural history of the disease, and response to treatment of hypophosphatemia.
Methods
Five CSHS subjects underwent prospective data collection at clinical research centers. A review of the literature identified 45 reports that included a total of 51 additional patients, in whom the findings were compatible with CSHS. Data on nevi subtypes, bone histology, mineral and skeletal disorders, abnormalities in other tissues, and response to treatment of hypophosphatemia were analyzed.
Results
Fractures, limb deformities, and scoliosis affected most CSHS subjects. Hypophosphatemia was not present at birth. Histology revealed severe osteomalacia but no other abnormalities. Skeletal dysplasia was reported in all anatomical compartments, though less frequently in the spine; there was no clear correlation between the location of nevi and the skeletal lesions. Phosphate and calcitriol supplementation was the most effective therapy for rickets. Convincing data that nevi removal improved blood phosphate levels was lacking. An age-dependent improvement in mineral abnormalities was observed. A spectrum of extra-osseous/extra-cutaneous manifestations that included both benign and malignant neoplasms was present in many subjects, though osteosarcoma remains unreported.
Conclusion
An understanding of the spectrum, natural history, and efficacy of treatment of hypophosphatemia in CSHS may improve the care of these patients.
Studies investigating the efficacy of lasers to minimize early surgical scars are low powered and report variable results. To further examine the evidence, the authors performed a systemic review and ...meta-analysis.
To present the evidence of randomized controlled trials investigating the efficacy of laser modalities in minimizing surgical scars when applied <1 month after operation.
A literature search of PubMed, EMBASE, Northern Light Life Sciences Conference Abstracts, and Cochrane Library was performed between November 6, 2015, and November 20, 2015. After assessing for inclusion, data extraction used the PRISMA checklist. Assessment for quality, validity, and risk of bias applied a scale devised by Jadad and colleagues, the Oxford Pain Validity Scale, and the RevMan risk of bias assessment tool, respectively. The GRADEpro application graded overall quality, and statistical analysis was performed with RevMan.
Approximately 4,373/4,397 abstracts and 16/24 full articles were excluded using predefined criteria, leaving 8 articles in the systematic review and 4 in the meta-analysis. The primary outcome reached statistical significance favoring the intervention group with standardized mean difference 0.39 (95% confidence interval, 0.05-0.74) and p = .03.
The outcome supports the efficacy of lasers in minimizing primarily closed surgical scars when treated <1 month after surgery.
Abstract
There is significant morbidity and mortality associated with the transmission of herpes simplex virus (HSV) from pregnant women to their fetus or newborn. Although most commonly transmitted ...in the peripartum period, in rare cases HSV can lead to intrauterine infection. Cutaneous lesions are the most common manifestation of intrauterine HSV, and have a wide spectrum of presentation. We present a rare case of intrauterine HSV-2 infection presenting with a zosteriform eruption mimicking congenital varicella syndrome in a newborn.
Pathologically elevated serum levels of fibroblast growth factor-23 (FGF23), a bone-derived hormone that regulates phosphorus homeostasis, result in renal phosphate wasting and lead to rickets or ...osteomalacia. Rarely, elevated serum FGF23 levels are found in association with mosaic cutaneous disorders that affect large proportions of the skin and appear in patterns corresponding to the migration of ectodermal progenitors. The cause and source of elevated serum FGF23 is unknown. In those conditions, such as epidermal and large congenital melanocytic nevi, skin lesions are variably associated with other abnormalities in the eye, brain and vasculature. The wide distribution of involved tissues and the appearance of multiple segmental skin and bone lesions suggest that these conditions result from early embryonic somatic mutations. We report five such cases with elevated serum FGF23 and bone lesions, four with large epidermal nevi and one with a giant congenital melanocytic nevus. Exome sequencing of blood and affected skin tissue identified somatic activating mutations of HRAS or NRAS in each case without recurrent secondary mutation, and we further found that the same mutation is present in dysplastic bone. Our finding of somatic activating RAS mutation in bone, the endogenous source of FGF23, provides the first evidence that elevated serum FGF23 levels, hypophosphatemia and osteomalacia are associated with pathologic Ras activation and may provide insight in the heretofore limited understanding of the regulation of FGF23.
Dermatologically, FGFR3 mutations can lead to acanthosis nigricans (AN), epidermal nevi, and seborrheic keratosis. A recent case report found that topical rapamycin (sirolimus) can improve ...FGFR3‐induced epidermal nevi with AN features in children, specifically with Fitzpatrick skin type (FST) I/II, and we would like to expand these findings to skin plaques with extensive AN‐like features in the FST IV/V adolescent population. An 18‐year‐old female with FST IV/V and FGFR3‐induced hypochondroplasia presented to our clinic with extensive AN‐like plaques. Significant improvement with lightening and thinning of the plaques was observed after applying 1% topical rapamycin cream twice daily. Topical rapamycin should be considered as a treatment option for AN, particularly in FST IV/V adolescents with FGFR3‐induced AN.
We report a pediatric case of extensive, progressive benign cephalic histiocytosis (BCH) involving the face, trunk, and extremities with response of facial lesions to treatment with topical 1% ...rapamycin. A split‐face model was used to demonstrate improvement on the treated side versus the untreated side. After physician and parental perception of effectiveness, based in part on photodocumentation, subsequently both cheeks were treated with continued improvement.
Sirolimus has emerged as a promising treatment for complex congenital vascular malformations but is limited because of systemic side effects. Topically compounded formulations, which have been found ...to be successful in the treatment of several other conditions, are a preferred drug delivery system to provide local therapy. We report a case of a venolymphatic malformation in an adolescent girl treated with topical 1% sirolimus cream leading to improvement in appearance and associated symptoms.
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