[Syphilis hepatitis and liver transplantation]. / Hépatite à syphilis et transplantation hépatique.

We report a case of secondary syphilis hepatitis in a liver-transplant patient. This homosexual male patient presented, 15 years after orthotopic liver transplantation, with non-squamous papulomacular rash, mild cytolysis, and anicteric cholestasis. Laboratory tests showed syphilis seroconversion with a venereal diseases research laboratory (VDRL) titer of 1/256, a Treponema pallidum hemaglutination assay (TPHA) of 1/5120, and a positive IgM fluorescent Treponemal antibody absorbance (FTA-abs). A liver biopsy performed 13 months after the diagnosis showed low-grade hepatitis with a Metavir score of A1F1; it also showed non-specific portal moderate inflammation consisting primarily of neutrophils, with no evidence of cholestasis. He was given benzathine-penicillin at 2,400,000 IU with a transient increase in prednisolone doses. Cytolysis rapidly, and cholestasis progressively disappeared. IgM FTA-abs became negative, whereas VDRL and TPHA titers decreased slightly over time.

[Trichothiodystrophy and congenital heart disease in two sisters]. / Trichothiodystrophie et cardiopathie congénitale chez deux soeurs.

INTRODUCTION: Trichothiodystrophy refers to a heterogeneous group of autosomal recessive genodermatosis of unknown etiology. Patients with trichothiodystrophy have alopecia with typical hair dysplasia ("tiger-tail"), and abnormally low sulfur content. Numerous unrelated neuroectodermal defects have been observed in trichothiodystrophy. We report here trichothiodystrophy and congenital heart disease in two sisters. CASES REPORT: Two sisters were born as collodion babies and presented ichthyosis and alopecia. The diagnosis of trichothiodystrophy was confirmed by polarizing microscopy of hair and low sulfur content. Both had congenital heart disease. DISCUSSION: Cardiovascular defects have rarely been reported in trichothiodystrophy. The association trichothiodystrophy - congenital heart disease has never been described. The low incidence of both conditions suggests that these abnormalities are linked etiologically rather than by chance. Abnormal Notch signaling, or contiguous gene deletion syndrome could lead to combined phenotype as observed in our family.

[Xerosis]. / La xérose.

The clinical characteristic of xerosis is rough or coarse skin. Physiopathologically, the structure of the stratum corneum is modified and abnormalities in keratinization, proliferation, surface lipid, water metabolism and also pH and sebum exist. There are two forms of xerosis: dry skin forms and ichtyosis or ichtyosis-like forms. Xerosis has many etiologies including external aggression, senescence, drugs, infection, atopy, deficiencies, malignant diseases, endocrine affections, eating disorders and renal failure in dialyzed patients. It provokes cutaneous discomfort and unaesthetic appearance that justify appropriate treatment. Treatment is essentially local, symptomatic and must be accompanied by general measures. Many products include moisturizers and emollients (keratolytics: salicylic acid, urea and alpha-hydroxy acid).

Acantholytic dyskeratotic epidermal nevus: a rare histopathologic feature.

BACKGROUND: Epidermal nevus is a congenital malformation of the epidermis consisting of verrucoid scaly plaques on the skin, often in a linear fashion. Different histologic features have been seen and, at times, acantholytic dyskeratosis has been observed. We report a new case of acantholytic dyskeratotic epidermal nevus. CASE REPORT: A 3-year-old girl presented, since birth, asymptomatic keratotic scaly lesions on the left hemithorax and left arm that followed Blaschko's lines. HISTOLOGY: Biopsies revealed acanthosis, papillomatosis, hyperkeratosis and focal areas of suprabasal clefting with acantholysis, as well as individual dyskeratotic cells (corps ronds et grains) in the upper layers of the epidermis. In the literature, this histologic feature has been reported twice. Generalized or localized Darier's disease are well-established clinical entities with characteristic histologic features of acantholytic dyskeratosis. Because of the linear clinical appearance and the onset at birth or early childhood, the lesions should be regarded as epidermal nevi and not linear Darier's disease. CONCLUSION: We report here an additional case of dyskeratotic epidermal nevus, which is a rare histopathologic feature.

[Sodium valproate-induced kinky hair]. / Cheveux crépus acquis induits par le valproate de sodium.

BACKGROUND: We report a case of acquired progressive kinking hair, a rare pilar dysplasia. This is the first case induced by sodium valproate. CASE REPORT: A 6-year-old girl, treated with valproate, observed a progressive change in the texture of her hair. They were kinky, lusterless, dry and, under light microscopy, exhibited an aspect of pseudo-pili torti. DISCUSSION: This child had acquired progressive kinking hair syndrome most likely induced by valproate. Five other cases of valproate-induced pilar dysplasia have been reported but without clinical descriptions. CONCLUSION: We propose adding sodium valproate to the list of drugs susceptible of inducing kinky hair syndrome.

[Eruptive pseudoangiomatosis in an adult renal transplant recipient]. / Pseudo-angiomatose éruptive chez un adulte transplanté rénal.

BACKGROUND: In 1969, Cherry et al. described four children with acute onset angioma-like papules with spontaneous regression during an acute viral infection. Similar cases, called eruptive pseudoangiomatosis, have been reported since and considered to be a viral exanthema. We observed a similar eruption in a 48-year-old male kidney transplant recipient. CASE REPORT: One month after kidney transplantation, the patient rapidly developed macules and papules on the trunk. He had unexplained fever 15 days before the eruption. A biopsy specimen revealed dermal blood vessels surrounded by lymphoid infiltrate. Serology tests were unable to identify any virus. The lesions resolved spontaneously within 15 days. DISCUSSION: In our patient, eruptive pseudoangiomatosis was diagnosed on the basis of the clinical and histological features and the disease course. This case demonstrates that the entity is not limited to children. Further cases should be studied to determine the precise pathogenics of this uncommon entity.

Identification of pancreatic type I secreted phospholipase A2 in human epidermis and its determination by tape stripping.

Phospholipases A2 (PLA2) catalyse the release of fatty acids from the sn-2 position of phospholipids and have been suggested to play a key part in permeability barrier homeostasis. Using a sensitive and versatile fluorometric method, significant PLA2 activity has been detected in both human skin homogenates and tape strippings of stratum corneum. Based on various properties (resistance to heat and sulphuric acid treatment, neutral optimal pH, absolute requirement for millimolar calcium concentrations, inhibition by dithiothreitol and p-bromophenacyl bromide, and resistance to a trifluoromethyl ketone derivative of arachidonic acid, AACOCF3, a specific inhibitor of cytosolic PLA2), this enzyme was characterized as a secretory PLA2 (sPLA2). Immunohistochemistry revealed strong labelling of type I pancreatic sPLA2 at the stratum corneum-stratum granulosum junction, type II sPLA2 being undetectable. An increase in PLA2 activity in tape-stripped material from the deepest level of the stratum corneum was correlated with partial morphological disappearance of type I sPLA2 immunolabelling. Our data thus provide the first convincing evidence that pancreatic sPLA2 is significantly expressed in human epidermis, where it might participate in the accumulation of free fatty acids contributing to the permeability barrier. In addition, our method for determining PLA2 activity in easily available tape strippings should allow further clinical studies aimed to explore possible PLA2 abnormalities in various dermatoses.

Localization of the Netherton syndrome gene to chromosome 5q32, by linkage analysis and homozygosity mapping.

Netherton syndrome (NS [MIM 256500]) is a rare and severe autosomal recessive disorder characterized by congenital ichthyosis, a specific hair-shaft defect (trichorrhexis invaginata), and atopic manifestations. Infants with this syndrome often fail to thrive; life-threatening complications result in high postnatal mortality. We report the assignment of the NS gene to chromosome 5q32, by linkage analysis and homozygosity mapping in 20 families affected with NS. Significant evidence for linkage (maximum multipoint LOD score 10.11) between markers D5S2017 and D5S413 was obtained, with no evidence for locus heterogeneity. Analysis of critical recombinants mapped the NS locus between markers D5S463 and D5S2013, within an <3.5-cM genetic interval. The NS locus is telomeric to the cytokine gene cluster in 5q31. The five known genes encoding casein kinase Ialpha, the alpha subunit of retinal rod cGMP phosphodiesterase, the regulator of mitotic-spindle assembly, adrenergic receptor beta2, and the diastrophic dysplasia sulfate-transporter gene, as well as the 38 expressed-sequence tags mapped within the critical region, are not obvious candidates. Our study is the first step toward the positional cloning of the NS gene. This finding promises a better understanding of the molecular mechanisms that control epidermal differentiation and immunity.

Inhibitory effects of retinoids on vascular endothelial growth factor production by cultured human skin keratinocytes.

BACKGROUND: Vascular endothelial growth factor (VEGF), a potent angiogenic factor and vasodilator, is strongly expressed by epidermal keratinocytes in many angiogenesis-dependent skin disorders. Retinoids may modulate VEGF in skin and this may be related to an effect on rosacea. AIM: To investigate the effect of retinaldehyde on VEGF production by human keratinocytes. METHODS: The effects of different concentrations of retinoids (all-trans-retinal and all-trans-retinoic acid) on VEGF production by cultured human skin keratinocytes in both cell extracts and supernatants were determined. Expression of VEGF was analyzed by enzyme-linked immunosorbent assay (ELISA) and RT-PCR. RESULTS: The amount of cell-associated and secreted VEGF strongly decreased with retinoid concentration (e.g. 48, 69% inhibition at 0.1 microM all-trans-retinal and -retinoic acid, respectively, in the supernatants). In parallel, approximately 25% inhibition of VEGF mRNA expression was obtained in the presence of 0.01 microM all-trans-retinal. CONCLUSION: The decrease in VEGF expression by keratinocytes on contact with retinoids may prevent skin neoangiogenesis in certain skin diseases.

In vitro main pathways of steroid action in cultured hair follicle cells: vascular approach.

The known role of steroids on the hair follicle leads us to investigate their effects on hair follicle cell angiogenic responses in vitro. We verified, using the immunohistochemical technique, whether human occipital scalp follicle cells express steroid receptors in vitro. We showed that androgen and estrogen receptors were expressed by dermal papilla cells (DPC) and keratinocytes from the outer root sheath in vitro. With regard to steroidal enzymes (type I and II 5alpha-reductases and Cytochrome-p-450-aromatase), the type I 5alpha-reductase gene is much more expressed in DPC than in dermal fibroblasts; however, the type II 5a-reductase gene is transcribed more in dermal fibroblasts than in DPC. The transcription of the two 5alpha-reductase isoform genes in cultured DPC is regulated by a 5alpha-reductase inhibitor. We also demonstrated that DPC, dermal fibroblasts, and outer root shealth keratinocytes expressed cytochrome-p-450-aromatase. Using ELISA and reverse transcriptase-polymerase chain reaction, we investigated the role played by some steroids (estrogens, androgens, antiandrogens) in the modulation of vascular endothelial growth factor (VEGF) expression by DPC. The association of different treatments of DPC (5alpha-reductase inhibitor and androgen receptor antagonist) shows a great stimulation of VEGF and aromatase expression. Strong stimulation of VEGF protein and gene expression is observed in the presence of 17beta-estradiol. Also, the concentration-dependent inhibition of VEGF expression by DPC using the cytochrome-p-450-aromatase inhibitor, confirms the involvement of this estrogenic pathway in the regulation of VEGF expression in vitro.

Minoxidil upregulates the expression of vascular endothelial growth factor in human hair dermal papilla cells.

The hair follicle dermal papilla which controls hair growth, is characterized in the anagen phase by a highly developed vascular network. We have demonstrated in a previous study that the expression of an angiogenic growth factor called vascular endothelial growth factor (VEGF) mRNA varied during the hair cycle. VEGF mRNA is strongly expressed in dermal papilla cells (DPC) in the anagen phase, but during the catagen and telogen phases. VEGF mRNA is less strongly expressed. This involvement of VEGF during the hair cycle allowed us to determine whether VEGF mRNA expression by DPC was regulated by minoxidil. In addition, the effect of minoxidil on VEGF protein synthesis in both cell extracts and DPC-conditioned medium, was investigated immunoenzymatically. Both VEGF mRNA and protein were significantly elevated in treated DPC compared with controls. DPC incubated with increasing minoxidil concentrations (0.2, 2, 6, 12 and 24 mumol/L) induced a dose-dependent expression of VEGF mRNA. Quantification of transcripts showed that DPC stimulated with 24 mumol/L minoxidil express six times more VEGF mRNA than controls. Similarly, VEGF protein production increases in cell extracts and conditioned media following minoxidil stimulation. These studies strongly support the likely involvement of minoxidil in the development of dermal papilla vascularization via a stimulation of VEGF expression, and support the hypothesis that minoxidil has a physiological role in maintaining a good vascularization of hair follicles in androgenetic alopecia.

[Pilar dysplasia: an early marker of giant axonal neuropathy]. / Dysplasie pilaire: un marqueur précoce de la neuropathie à axones géants.

BACKGROUND: Giant axonal neuropathy is an autosomal recessive condition characterized by progressive degeneration of the central and peripheral nervous system. Sensoromotor neuropathy develops around 3 years of age. Children have particular faces with curly hair. Characteristic pilar anomalies occur early and have diagnostic value. CARE REPORT: An Algerian boy born to consanguineous parents (first cousins) had language retardation and gait disorders developed around 3 years of age. At 9 years, the child was in a cachetic state with valgus feet, amyotrophy and diminished muscle force predominating distally, ataxia, areflexia, sensoromotor neuropathy and nystagmus. Skin tropism was altered with pale, thin and dry skin, cold, cyanotic limbs and thick curly hair. Electrophysiology explorations showed signs of chronic sensoromotor polyneuropathy with axonal predominance. Brain and spinal MRI revealed cerebellar atropy and signs of leukodystrophy. The spinal tap was normal. A neuromuscular biopsy confirmed the diagnosis of giant axonal neuropathy. At examination the hair was thick with reduced refrangibility and a pseudo-pili torti aspect. DISCUSSION: Giant axonal neurpathy is characterized by anomalous organization of the cytoskeleton of intermediary filaments in different types of cells. Hair anomalies occur early, before onset of neurological signs. At gross examination the hair is thick and curly, sometimes crimped and pale. Examination of the pilar shaft shows trichorrhexis nodosa, scalloped fringes and lack of internal structure. On the molecular level, there is a reduction in the number of bisulfur bridges which could be the cause of defective keratin filament alignement. Pathogenicaly, the pilar anomalies are considered as a direct manifestation of defective keratin organization characteristic of the disease.

Vascular endothelial cells: targets for studying the activity of hair follicle cell-produced VEGF.

Fetal bovine aortic endothelial cells (FBAEC) were exposed to purified fractions of conditioned medium from cultures of hair dermal papilla cells (DPC) to determine the existence of any vascular endothelial growth factor (VEGF)-like paracrine activity of the latter. Such fractions were tested for stimulation of growth and migration of cultured FBAEC. In addition, VEGF secretion by DPC was measured by radioassay of VEGF receptors using FBAEC as target cells. The results showed that stimulation of FBAEC proliferation and migration following exposure to purified conditioned medium was dose-dependent. Radioreceptor assays of recombinant VEGF and purified DPC-conditioned medium showed competitive VEGF binding in FBAEC.