The course of lichen sclerosus diagnosed prior to puberty.

STUDY OBJECTIVE: To help determine the long-term course of girls diagnosed with lichen sclerosus before puberty. DESIGN: Retrospective chart review and follow-up interview. SETTING: Washington University pediatric gynecology and dermatology clinics. PARTICIPANTS: Premenarchal girls diagnosed with lichen sclerosus from 1989-2010. INTERVENTIONS: Telephone interview. MAIN OUTCOME MEASURES: Resolution of symptoms, specifically pain and/or pruritus. RESULTS: Follow-up was available for 36 premenarchal girls. The mean age at lichen sclerosus (LS) diagnosis was 7 years (range: 3-14 years). The mean duration of follow-up was 5.3 years (range: 2 months-15 years). Treatment with topical steroids (primarily 0.05% clobetasol propionate ointment) resulted in improvement in symptoms within an average of 14 weeks (range: 2 weeks-2 years) in 33 girls. Eighty-three percent of patients (n = 30) experienced remission after initial treatment. Sixteen patients reported relapses requiring an average of 3.1 years of intermittent maintenance therapy. The mean length of remission to date was 3.6 years (range 1 months-10 years). 72% of patients reported remission at the time of the phone interview. Of note, 7 out of 9 patients in our study who continue to report symptoms are still premenarchal. One postmenarchal patient was asymptomatic but had signs of LS on physical exam. CONCLUSION: The prognosis and long term course of LS diagnosed prior to puberty is unclear. Although remission may occur prior to menarche in some cases, once children reach menarche with active disease, complete remission may be less likely. Treatment duration of LS in our study had a wide range, but 3 months appears to be adequate for most patients to obtain remission.

Topical cidofovir for refractory verrucae in children.

Warts are common and are a challenge to treat in some children, especially immunocompromised children and those who fail or cannot tolerate salicylic acid preparations and cryotherapy. Cidofovir, a nucleotide analogue with antiviral activity, has demonstrated promising results when compounded into a topical form to treat refractory warts. We present a retrospective institutional review of 12 children with refractory verrucae treated with 1% to 3% topical cidofovir compounded in an unscented moisturizing cream, applied every other day to daily. In our institutional series, only three patients (25%) demonstrated complete clearance of their verrucae. An additional four patients (33%) demonstrated partial clearance. Our experience using topical cidofovir has been less successful than previous institutional reviews, possibly because we used a lower concentration and less-frequent dosing. More studies are needed to better characterize the efficacy, safety, and dosing of topical cidofovir for the treatment of refractory warts.

Morphologic features and natural history of scalp nevi in children.

OBJECTIVE: To characterize the clinical changes in clinically distinctive scalp nevi over time in children to help guide management and avoid misdiagnosis as melanoma. DESIGN: Cohort study. SETTING: Washington University School of Medicine pediatric dermatology clinics. Patients Of 93 patients younger than 18 years with photographically documented, clinically distinctive scalp nevi, 28 (30%) consented to participate. Minimum follow-up from the initial visit was 1 year. Collectively, these patients had 44 scalp nevi at the initial visit. No patient had a personal diagnosis of melanoma or dysplastic nevus syndrome. MAIN OUTCOME MEASURES: Clinical changes in scalp nevi as determined using the ABCDE scoring system (ie, asymmetry, border irregularity, color variegation, diameter >6 mm, and evolution/elevation from initial to follow-up images) on initial and follow-up photographs of scalp nevi. RESULTS: Overall, 77% of the clinically distinctive scalp nevi (34 of 44) showed clinical signs of change during mean follow-up of 2.8 years. Of those with changes, 18 (53%) became more atypical and 16 (47%) became less atypical since the initial examination. None of the changes were concerning for melanoma. The mean total scalp nevus count was 2.6. Scalp nevi represented approximately 6% of total-body nevi. The number of scalp nevi increased with age. Boys had 1.5 times the number of scalp nevi as girls (P = .03). CONCLUSIONS: Scalp nevi are clinically dynamic in childhood. These changes include an increase or a decrease in atypical features and occur in all age groups. This preliminary study does not support excisional biopsies but does support physician evaluation of scalp nevi evolution and serial photography of clinically distinctive lesions.

Retrovirus-polymer complexes: study of the factors affecting the dose response of transduction.

We have previously shown that complexes of Polybrene (PB), chondroitin sulfate C (CSC), and retrovirus transduce cells more efficiently than uncomplexed virus because the complexes are large and sediment, reaching the cells more rapidly than by diffusion. Transduction reaches a peak at equal weight concentrations of CSC and PB and declines when the dose of PB is higher or lower than CSC. We hypothesized that the nonlinear dose response of transduction was a complex function of the molecular characteristics of the polymers, cell viability, and the number of viruses incorporated into the complexes. To test this hypothesis, we formed complexes using an amphotropic retrovirus and several pairs of oppositely charged polymers and used them to transduce murine fibroblasts. We examined the effect of the type and concentration of polymers used on cell viability, the size and charge of the complexes, the number of viruses incorporated into the complexes, and virus binding and transduction. Transduction was enhanced (2.5- to 5.5-fold) regardless of which polymers were used and was maximized when the number of positive charge groups was in slight excess (15-28%) of the number of negative charge groups. Higher doses of cationic polymer were cytotoxic, whereas complexes formed with lower doses were smaller, contained fewer viruses, and sedimented more slowly. These results show that the dose response of transduction by virus-polymer complexes is nonlinear because excess cationic polymer is cytotoxic, whereas excess anionic polymer reduces the number of active viruses that are delivered to the cells.

Rapid concentration and purification of retrovirus by flocculation with Polybrene.

We have previously shown that the combined addition of Polybrene (PB) and chondroitin sulfate C (CSC) to retrovirus stocks leads to the formation of retrovirus-polymer complexes (i.e., flocs) that rapidly sediment onto cells, increases the efficiency of gene transfer, and can be used to rapidly concentrate and purify retrovirus stocks. The viruses remain associated with the polyelectrolyte complexes, however, which may complicate their use in downstream applications. In this study we determined if retrovirus could be flocculated using only one polymer (PB). We found that when retrovirus stocks were incubated with 320 microg/ml of PB, more than 70% of the viruses, and fewer than 0.3% of all other proteins, were pelleted by low-speed centrifugation. In contrast to retrovirus complexes formed with two polymers, retrovirus flocculated with PB disaggregated when they were resuspended in fresh medium. We conclude that flocculation of retroviruses with a single cationic polymer (PB) is a useful method for rapidly concentrating and purifying retroviruses, and may prove particularly useful when it is desirable to generate purified virus that is not part of a polymer complex.