Novel and recurrent germline LEMD3 mutations causing Buschke-Ollendorff syndrome and osteopoikilosis but not isolated melorheostosis.

Mutations in the LEMD3 gene were recently incriminated in Buschke-Ollendorff syndrome (BOS) and osteopoikilosis, with or without melorheostosis. The relationship of this gene with isolated sporadic melorheostosis is less clear. We investigated LEMD3 in a two-generation BOS family showing an extremely variable expression of the disease, in a sporadic patient with skin features of BOS, and in an additional subject with isolated melorheostosis. We identified two different mutations, both resulting in a premature stop codon, in the two cases of BOS. The mutation (c.2564G>A) reported in the familial case is novel, while that observed in the sporadic case (c.1963C>T) has been previously reported in an American woman with osteopoikilosis and melorheostosis who had a family history of isolated osteopoikilosis. The search for mutations in DNA extracted from the peripheral blood, as well as skin and bone biopsies of the patient with melorheostosis failed to identify any pathogenic change. Our results further expand the LEMD3 mutation repertoire, corroborate the extreme interfamilial and intrafamilial clinical variability of LEMD3 mutations, and underline the lack of a clear phenotype-genotype correlation in BOS. The present study supports the general conclusion that LEMD3 mutations do not contribute to isolated sporadic melorheostosis. The genetic or epigenetic influences that are responsible for the development of melorheostosis require further investigation.

Survival and prognostic factors in patients with localised cutaneous melanoma observed between 1980 and 1991 at the Istituto Dermopatico dell'Immacolata in Rome, Italy.

530 patients with localised cutaneous melanoma consecutively observed between 1980 and 1991 at a hospital for skin diseases in Rome, Italy, were studied. Crude survival proportions were calculated with the method of Kaplan and Meier. Cox proportional hazards regression analysis was used to estimate the effect of prognostic factors on death rates. Females and younger patients had better 5- and 10-year survival rates, while increasing tumour thickness was associated with a decrease in survival time. In the multivariate analysis, an independent association with survival was found for tumour thickness, presence of ulceration, age, sex and cross-sectional profile of neoplasia. Our study confirms that females and young patients with thin melanomas have a better prognosis, while the importance of cross-sectional profile needs further study.

Mother-to-child transmission of human immunodeficiency virus type 1: risk of infection and correlates of transmission.

One thousand eight hundred eighty-seven children born to human immunodeficiency virus type 1 (HIV-1) seropositive mothers, including 1045 infants prospectively followed up from birth, were studied. Intravenous drug use was the most frequent maternal risk factor, although the percentage of women infected by sexual contact increased from 5.8% in 1985 to 28.5% in 1990. Of the 551 first children followed up from birth and older than 15 months of age, 101 (18.3%) acquired infection and seroconverted to HIV-1. Another 31 (5.6%) asymptomatic seronegative children showed the presence of viral markers, for an apparent mother-to-offspring transmission rate of 23.9%. Overlapping results were seen in 22 second-born children followed up from birth. Of 59 sibships with definite infection status, when the first child was infected, 14 (40%) of 35 second children were infected, whereas when the first child was not infected, only 2 of 24 (8.3%) second children were infected. Discordance in HIV-1 transmission was found in 1 of 18 pairs of twins. Univariate and multivariate analyses of possible risk factors for HIV-1 transmission performed on the entire population of children and in the cohort of those followed up from birth were basically in agreement in indicating that the development of symptoms in the mother before delivery and breast-feeding (indeed adopted in only 22 infants in whom HIV-1 infection was identified at birth) were significantly and independently associated with a higher transmission rate. In addition, girls were more frequently infected than boys.(ABSTRACT TRUNCATED AT 250 WORDS)

In situ labelling of fragmented DNA in cutaneous necrotizing vasculitis.

Apoptosis is a biochemically and morphologically gene-regulated distinctive form of cell death playing a pivotal role in tissue homeostatic, viral infections and clearance of damaged cells. The process is initiated by a cascade of intercellular and intracellular signals through an intrinsic cell suicide program resulting in early DNA fragmentation characterized by nuclear and cytoplasmic condensation. Recently some authors have reported apoptosis to occur in several inflammatory skin diseases, such as lichenoid reactions and cutaneous lymphomas. The aim of our study is to investigate the apoptotic phenomenon in two different forms of cutaneous necrotizing vasculitis (CNV) affecting the postcapillary venules such as leukocytoclastic and lymphocytic cutaneous vasculitis. For this purpose, the in situ nick end labelling of fragmented DNA technique has been performed on lesional skin biopsies from patients with acute phase of the disease. In both leukocytoclastic and lymphocytic forms apoptotic bodies were detected, evidencing two different characteristic patterns of distribution, probably related to the different nature of cellular inflammatory infiltrate. Our results seem to account for the involvement of apoptotic phenomena in cutaneous vasculitis; furthermore, the evaluation of in situ DNA fragmentation could be a useful tool to discriminate different forms of the disease.

Pruritic eosinophilic papular eruption revealing HIV infection.

Eosinophilic folliculitis (EF) is a rare follicular pruritic papular eruption observed in association with human immunodeficiency virus (HIV). The diagnosis of eosinophilic folliculitis is based on the histologic findings consisting of a sterile inflammatory infiltrate rich in eosinophils involving hair follicles. EF in HIV patients is believed to be an immunoinflammatory response directed either at follicular or skin flora antigens in the late-stage of HIV infection. In this stage, immune response is characterized by a shift from a Th1- to a Th2-dominant cytokine profile and an increased secretion of interleukin-4 and interleukin-5, both known to promote eosinophilia. We describe a case of HIV-associated eosinophilic folliculitis in a 30-year-old black woman referred to us for a pruritic follicular eruption without any other clinical symptom related to the acquired immunodeficiency syndrome. HIV infection presenting with EF has been rarely reported and its occurrence in women is also very rare.

Unilateral demodicidosis.

A 45-year-old man presented with a unilateral, papulopustular, rosacealike, chronic dermatitis which involved the left portion of the forehead and the eyelids unilaterally. Many Demodex mites were found in the follicles of the affected area. Topical crotamiton cleared the lesions after an unsuccessful trial with oral metronidazole. This observation provides further evidence that demodicidosis is a condition distinct from common rosacea.

Time trends in features of cutaneous melanoma at diagnosis: central-south Italy, 1962-1991.

A total of 1360 cases of cutaneous malignant melanoma (CMM) consecutively diagnosed at the Istituto Dermopatico dell'Immacolata (IDI) in Rome, during the period 1962-1991, were reviewed. There was a positive trend of thin (Breslow thickness < 1.49 mm) lesions at diagnosis in comparison to thick lesions, with more severe prognosis (p < 0.05). CMM on the trunk and upper legs increased more than CMM on the face (p < 0.05). There are suggestions that the incidence of CMM in the hospital referral population, resident in Central-South Italy, has been steadily rising. This trend could be due not only to a referral bias related to a growing public concern about "bad moles", but also to a real increase in the incidence of CMM.

[Histological simulators of Kaposi's sarcoma in the initial phase]. / I simulatori istologici del sarcoma di Kaposi nella fase iniziale.

Early Kaposi's sarcoma might be simulated by many different conditions, especially when the vascular component is prominent. the criteria suggested to differentiate early Kaposi's simulators are discussed. We found that these criteria are high in sensibility but low in specificity, therefore, we suggest using these criteria only when they are found in clusters.

Prenatal diagnosis of a fetus with an extra idic(X)(q27).

A fetus with an extra idic(X)(q27) was ascertained during prenatal diagnosis. The derived X and one normal X chromosome were late replicating. Due to lack of previous experience, genetic counselling presented obvious difficulties and the fetal phenotype could be only tentatively predicted.

Long-term epilation with long-pulsed neodimium:YAG laser.

BACKGROUND: Unwanted body hair can represent a severe cosmetic disturbance. The traditional methods used to epilate often have limitations, side effects, and unsatisfactory results. In recent years, various light sources (lasers and others) have been developed for long-term epilation of unwanted hair. OBJECTIVE: This study evaluates, on a large number of patients, the efficiency and safety of a long-pulsed low-potency Nd-Yag laser invented specifically for long-term hair removal. METHODS: Some 208 subjects needing epilation were divided into three groups and treated during an 11-month period. Group A included 79 patients with a normal distribution of unwanted hair; Group B 67 patients with constitutional hypertrichosis; and Group C 62 patients with hirsutism. Treatment sessions were performed with a fluence of 23-56 J/cm2 at 1-month intervals until obtaining desirable results. Follow-ups ranged from 1 to 6 months. In 3 patients 4-mm diameter punch biopsy specimens were obtained before the first session and again after 6 hours. A third biopsy was performed after 3 months. RESULTS: Every session resulted in a 20-40% hair loss, depending on the color of hair. Complete epilation was obtained in 4 to 6 sessions. Only white hair was not receptive to laser light, and its growth was not modified. No patients, including dark-complexioned patients, had blistering, hypo-or hyperpigmentation. No pain was present during treatment except for the axillary area. In the specimen obtained after 6 hours, very extensive necrosis of the hair follicular and sebaceous gland epithelium was evident. Histologic findings of the biopsies taken after three months showed complete disappearance of hair and moderate fibrosis. CONCLUSION: This study proves that the long-pulsed Nd:Yag laser treatment produces an excellent prolonged epilation with no relevant side effects. This laser light, having a 1064 nm wavelength, is minimally absorbed in superficial skin layers, and pronounced scattering up to 5 mm occurs targeting the deeper follicles.

The possibility of prenatal diagnosis by gene dosage: confirmation of duplication 10q24 to qter from GOT-1 activity in fetal erythrocytes.

The activity of four enzymes, including GOT-1, has been investigated in he erythrocytes of a 10q to 24 qter trisomic fetus. Analyses have been performed on a feto-maternal blood mixture sampled by fetoscopy and on red cells obtained by cardiac puncture, following therapeutic abortion. The demonstration of a 40 per cent increase of GOT-1 activity, as compared to normal fetuses of similar gestational age, suggests that gene dosage studies may be a useful confirmatory technique in prenatal diagnosis of unbalanced chromosomal aberrations. Practical application of a similar diagnostic approach is conditioned by (1) precise characterization of fetal chromosome imbalance; (2) confirmed assignment of the gene locus coding for the gene product under investigation; (3) evidence of a linear proportionality between gene dose and concentration of the gene product in patients with the same chromosome imbalance detected in the fetus; (4) knowledge of the range of normal variation at different weeks of gestation of the enzyme activity to be tested in the fetus; (5) safety of fetal sampling procedure.

First trimester monitoring of a pregnancy at risk for glucose phosphate isomerase deficiency.

First trimester prenatal diagnosis was offered to the mother of a child affected by severe haemolytic anaemia due to glucose phosphate isomerase (GPI) deficiency. The mutant enzyme was characterized by an increased thermal lability. Both parents had 50 per cent normal red cell GPI activity. We have shown that the homozygous and heterozygous genotypes can be clearly distinguished from each other and controls by combinations of the measurement of enzyme activity and enzyme thermal lability. Examination of trophoblast cells obtained at 9 weeks of gestation led to the diagnosis of a GPI heterozygous fetus. The result was confirmed by analysis on uncultured and cultured amniotic fluid cells sampled at 16 weeks and by red blood cell studies of the healthy newborn. Prenatal diagnosis of GPI deficiency is indicated in families with previous cases resulting in severe haemolysis and mainly with the conservative view of arranging appropriate therapeutic measures for affected fetuses.

Pigmented purpura-like eruption as cutaneous sign of mycosis fungoides with autoimmune purpura.

We describe the clinical and laboratory findings of a young man with mycosis fungoides. The disease was associated, since the early stages, with autoimmune purpura. Interferon alfa (IFN-alpha) administration improved this patient's condition, both the purpuric eruption and patchy cutaneous lesions, thus suggesting T-cell abnormalities may be responsible for the development of the disease.

Eruptive pseudoangiomatosis.

Eruptive pseudoangiomatosis is a rare, benign, spontaneously regressive disease. The term was recently coined to describe a dermatosis characterized by the sudden onset of a few to several bright red angioma-like papules with histopathologic findings distinct from that of true angiomas. We describe a 7-year-old patient with the typical lesions of eruptive pseudoangiomatosis.

Monitoring of pregnancies at risk for Fanconi's anemia by chorionic villi sampling.

Two pregnancies at risk for Fanconi's anemia have been monitored by a cytogenetic method in the first trimester of gestation. The rate of chromosome breakage was evaluated in spontaneous mitoses from a direct preparation of trophoblasts in one case and from mitoses obtained from standard cultures and from mitoses treated with diepoxybutane in both cases. Cytogenetic studies were carried out also at 16 weeks from amniotic fluid cells in one case, and in fibroblasts sampled from the aborted fetus in the other. In all the experimental conditions the mean frequency of breaks/cell was in the range of controls, suggesting that the fetuses were unaffected by Fanconi's anemia. In one case the results have been confirmed by chromosome analysis at birth.

Discordant sex in one of three monozygotic triplets.

A case is reported of monozygotic triplets, discordant for phenotypic sex, in which the female presented at birth with the features of Turner's syndrome. Chromosomal analyses showed homogeneous 46,XY karyotypes in the lymphocytes of the three sibs, while a 45,X non-mosaic chromosome constitution was detected in skin fibroblasts of the female triplet. It is suggested that mitotic non-disjunction or anaphase lag occurring early during embryonic development accounted for the occurrence of monosomy X in one cell line of the affected triplet. Previous observations of monozygotic twin pairs discordant for chromosome constitutions are reviewed.