Invisible metallic microfiber in clothing presents unrecognized MRI risk for cutaneous burn.

SUMMARY: We report a case of a thermal burn that occurred during MR imaging likely caused by invisible silver-embedded microfibers in the fabric of an undershirt. As the prevalence of fabric containing nondetectable metallic microfiber increases in athletic and "tech" clothing, the importance of having patients change into safe facility-provided garments before MR imaging is emphasized.

Pregnancy and obstetrical outcomes in pseudoxanthoma elasticum.

BACKGROUND: Pseudoxanthoma elasticum (PXE) is a genetic multisystem disorder characterized by calcified dystrophic elastic fibres in skin, retina and arteries. Much of the earlier literature on pregnancy in PXE contained reports of severe complications, leading some healthcare providers to advise women with PXE against becoming pregnant and some women with PXE to avoid pregnancy. OBJECTIVES: To evaluate the obstetrical outcomes and the incidence of pregnancy complications in women with PXE and to determine if pregnancy is associated with an adverse effect on the course of the disease. METHODS: Women with PXE (n = 407) answered detailed questionnaires regarding reproductive history and pregnancy as well as the course of their disease. The frequency of reported pregnancy outcomes and complications was determined. Severity indices for the major clinical manifestations of PXE were developed and correlated with gravidity of affected women aged 40 years or over. RESULTS: Among the 306 respondents with PXE who had ever been pregnant, there were 795 pregnancies. Of these, 83% ended in live births and 1% in stillbirth. The median birth weight was within the normal range and the incidence of low birth weight for gestation was low. Hypertension occurred in 10% of pregnancies, gastric bleeding and retinal complications in < 1%, and 12% of pregnancies were associated with worsening of skin manifestations. There was no effect of gravidity and clinical severity on cutaneous (P = 0.07), ocular (P = 0.59) or cardiac (P = 0.42) manifestations of PXE in women aged 40+ years, nor did ever having been pregnant adversely affect these clinical severity indices. Of the 101 women who had never been pregnant, 17% made the decision because they were advised against becoming pregnant by a healthcare professional and 11% did not become pregnant because they feared an adverse outcome either in their pregnancy or disease. CONCLUSIONS: PXE is not associated with markedly increased fetal loss or adverse reproductive outcomes. The incidence of gastric bleeding, although probably higher than in the unaffected population, is much lower than previously reported, and retinal complications are uncommon. Although a few pregnancies were associated with worsening of skin manifestations, there was no correlation of either gravidity or ever having been pregnant with ultimate severity of skin, ocular or cardiovascular manifestations. There is no basis for advising women with PXE to avoid becoming pregnant, and most pregnancies in PXE are uncomplicated.

A spectrum of ABCC6 mutations is responsible for pseudoxanthoma elasticum.

To better understand the pathogenetics of pseudoxanthoma elasticum (PXE), we performed a mutational analysis of ATP-binding cassette subfamily C member 6 (ABCC6) in 122 unrelated patients with PXE, the largest cohort of patients yet studied. Thirty-six mutations were characterized, and, among these, 28 were novel variants (for a total of 43 PXE mutations known to date). Twenty-one alleles were missense variants, six were small insertions or deletions, five were nonsense, two were alleles likely to result in aberrant mRNA splicing, and two were large deletions involving ABCC6. Although most mutations appeared to be unique variants, two disease-causing alleles occurred frequently in apparently unrelated individuals. R1141X was found in our patient cohort at a frequency of 18.8% and was preponderant in European patients. ABCC6del23-29 occurred at a frequency of 12.9% and was prevalent in patients from the United States. These results suggested that R1141X and ABCC6del23-29 might have been derived regionally from founder alleles. Putative disease-causing mutations were identified in approximately 64% of the 244 chromosomes studied, and 85.2% of the 122 patients were found to have at least one disease-causing allele. Our results suggest that a fraction of the undetected mutant alleles could be either genomic rearrangements or mutations occurring in noncoding regions of the ABCC6 gene. The distribution pattern of ABCC6 mutations revealed a cluster of disease-causing variants within exons encoding a large C-terminal cytoplasmic loop and in the C-terminal nucleotide-binding domain (NBD2). We discuss the potential structural and functional significance of this mutation pattern within the context of the complex relationship between the PXE phenotype and the function of ABCC6.

The placenta in pseudoxanthoma elasticum: clinical, structural and immunochemical study.

Pseudoxanthoma elasticum (PXE) is a rare genetic disorder clinically characterized by skin, cardiovascular and eye manifestations, mainly due to calcification and fragmentation of elastic fibres. Although infrequent, complications during pregnancy in women affected by PXE have been reported. The aim of the present study was to compare structural features of placentae at term from 14 control and 15 PXE-affected women, in order to better understand if and how abnormal mineral and/or matrix accumulation might affect placental function in PXE. In all cases, pregnancy, fetus growth and delivery were normal. Both gross and light microscopy examination did not reveal dramatic differences between placentae of PXE patients and controls, with regard to weight, dimensions, infarcts, thrombi, inflammatory lesions or vessels. However, necrotic changes and mineralization appeared statistically more pronounced in PXE. By electron microscopy the most remarkable differences between PXE and control placentae were observed in the localization and morphology of mineral precipitates; a significant higher deposition of mineral precipitates was observed associated with the "matrix"-type fibrinoid and among collagen fibrils, especially on the maternal side. Immunocytochemistry revealed the presence of vitronectin and fibronectin associated with the PXE-specific mineralizations and the absence of mineralization on the small and scarce elastic fibres in either controls or in PXE.

Pseudoxanthoma elasticum: significance of limited phenotypic expression in parents of affected offspring.

The inheritance pattern of pseudoxanthoma elasticum (PXE) is controversial. Inheritance patterns are confounded by delayed diagnosis and mild or limited phenotypic expression among certain family members. Because testing for the genetic mutation(s) responsible for PXE is not routine, genetic counseling must be done with caution. We describe 4 families in which one or more children were diagnosed with PXE. Detailed examination of the parents was carried out, including skin biopsy and ophthalmologic examination. In 3 of the 4 families, one parent had limited phenotypic expression, such as ocular findings without skin lesions or very mild skin lesions with no ocular findings. In the other family, one parent had very mild skin and ocular disease. All 4 affected parents had diagnostic skin biopsy findings. In none of the 4 families was the inheritance pattern clear-cut. Although the inheritance pattern of PXE has been debated, clinically significant stigmata of PXE, which are not always readily apparent, can occur in successive generations. Therefore all first-degree relatives of affected patients should receive a full dermatologic examination as well as a funduscopic examination. If even mild typical skin or eye findings are present, then skin biopsy should be performed.

Mutations in a gene encoding an ABC transporter cause pseudoxanthoma elasticum.

Pseudoxanthoma elasticum (PXE) is a heritable disorder characterized by calcification of elastic fibres in skin, arteries and retina that results in dermal lesions with associated laxity and loss of elasticity, arterial insufficiency and retinal haemorrhages leading to macular degeneration. PXE is usually found as a sporadic disorder, but examples of both autosomal recessive and autosomal dominant forms of PXE have been observed. Partial manifestations of the PXE phenotype have also been described in presumed carriers in PXE families. Linkage of both dominant and recessive forms of PXE to a 5-cM domain on chromosome 16p13.1 has been reported (refs 8,9). We have refined this locus to an 820-kb region containing 6 candidate genes. Here we report the exclusion of five of these genes and the identification of the first mutations responsible for the development of PXE in a gene encoding a protein associated with multidrug resistance (ABCC6).

Pseudoxanthoma elasticum maps to an 820-kb region of the p13.1 region of chromosome 16.

We have performed linkage analysis on 21 families with pseudoxanthoma elasticum (PXE) using 10 polymorphic markers located on chromosome 16p13.1. The gene responsible for the PXE phenotype was localized to an 8-cM region of 16p13.1 between markers D16S500 and D16S3041 with a maximum lod score of 8.1 at a recombination fraction of 0.04 for marker D16S3017. The lack of any locus heterogeneity suggests that the major predisposing allele for the PXE phenotype is located in this region. Haplotype studies of a total of 36 PXE families identified several recombinations that further confined the PXE gene to a region (< 1 cM) between markers D16S3060 and D16S79. This PXE locus was identified within a single YAC clone and several overlapping BAC recombinants. From sequence analysis of these BAC recombinants, it is clear that the distance between markers D16S3060 and D16S79 is about 820 kb and contains a total of nine genes including three pseudogenes. We predict that mutations in one of the expressed genes in the locus will be responsible for the PXE phenotype in these families.

Topical chemotherapy of actinic keratoses of the upper extremity with tretinoin and 5-fluorouracil: a double-blind controlled study.

In a randomized double-blind controlled study, 19 patients applied 5% 5-fluorouracil (5-FU) cream to actinic keratoses (AK) on each arm twice daily, followed by nightly application of 0.05% tretinoin cream to one arm, and a control cream to the other arm until discomfort precluded further applications. After 3 months, the number of residual AK was compared to pre-treatment values. The tretinoin-treated arms had 15.7 +/- 6.1 AK before treatment and 3.4 +/- 2.6 AK following therapy. The control arms had 15.3 +/- 6.9 AK before therapy and 4.2 +/- 2.5 lesions afterwards. Using a one-tailed paired t-test, the difference in response was statistically significant (0.03 less than P less than 0.04). It was concluded that daily application of 0.05% tretinoin cream appeared to enhance the efficacy of topical 5-FU in destruction of AK of the arms and may represent a useful treatment modality.

Pustular herpes gestationis.

Pustular eruptions during pregnancy and the puerperium are rare. A case of herpes gestationis (HG) in which the lesions were predominantly pustules and in which a vesicular or bullous component was not noted is reported. The differential diagnosis of pustular eruptions associated with pregnancy is discussed.

The natural history of congenital sutural cataracts. Case report with long-term follow-up.

A 21-year-old patient is presented in whom striking regression of congenital sutural cataracts and progression of lamellar cataracts were documented photographically over an 18-year period. These unexplained findings are at variance with the prevailing impression that congenital nuclear and sutural cataracts are stationary in postnatal life.

Ophthalmic features of chromosome deletion 4p- (Wolf-Hirschhorn syndrome).

By using the Giemsa banding technique we identified three patients with chromosome deletion 4p-. All had anterior segment anomalies, exotropia, blepharoptosis, antimongoloid palpebral fissures, hypertelorism, and disk abnormalities. One patient (Case 1) had Rieger's anomaly. Some clinical features in patients with 4p- are similar to those in patients with chromosome deletion 5p-, cri-du-chat syndrome, although 4p- individuals do not have the distinctive cry. The ocular features which distinguish 4p- from other deletions include normal tearing, some degree of blepharoptosis, and the preponderance of anterior segment signs.