Mutations in SPINK5, encoding a serine protease inhibitor, cause Netherton syndrome.

We describe here eleven different mutations in SPINK5, encoding the serine protease inhibitor LEKTI, in 13 families with Netherton syndrome (NS, MIM256500). Most of these mutations predict premature termination codons. These results disclose a critical role of SPINK5 in epidermal barrier function and immunity, and suggest a new pathway for high serum IgE levels and atopic manifestations.

[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.

Cholesterol sulfate is not degraded but does not accumulate in Epstein-Barr virus-transformed lymphoid cells from patients with X-linked ichthyosis.

The metabolism of cholesterol sulfate (CS) was investigated in immortalized, Epstein-Barr virus-transformed lymphoid cell lines derived from normal individuals and patients affected with recessive X-linked ichthyosis (XLI). Normal lymphoid cells expressed arylsulfatase C and steroid sulfatase (including cholesterol sulfatase) activities, and these two sulfohydrolases showed the same enzyme properties as in other human cells, e.g., leukocytes or skin fibroblasts. XLI-derived lymphoid cell lines exhibited extremely deficient activity of both arylsulfatase C and steroid sulfatase. While normal and XLI intact, living lymphoid cells could take up exogenous radiolabelled CS through a non-receptor-mediated process. XLI cells were completely unable to degrade CS to cholesterol. However, despite their defect in CS degradation, steroid sulfatase-deficient cells did not accumulate CS because of outflux of this sterol. The potential implications of these findings to the pathogenesis of increased CS content in plasma and epidermis of XLI patients are discussed. This study also demonstrates that immortalized lymphoid cell lines may represent a useful experimental model system for the study of XLI.

The gene for Bazex-Dupré-Christol syndrome maps to chromosome Xq.

Bazex-Dupré-Christol syndrome is an inherited condition with skin cancer predisposition characterized by follicular atrophoderma, hypotrichosis, and early onset of multiple basal cell carcinomas. Previous reports suggested an X-linked mode of inheritance. We therefore performed linkage analysis with microsatellite markers of the X chromosome in three families. We obtained evidence for X-linkage and regional assignment to Xq24-q27 of this syndrome (maximal lod score = 5.26 with a recombination fraction of 0% at the DXS1192 locus). This represents a first step towards the identification of a gene involved in hair follicle development and skin tumor formation.

Vascular endothelial growth factor is an autocrine growth factor for hair dermal papilla cells.

The transition of the late anagen to the catagen phase is concomitant with the disappearance of perifollicular capillaries, and therefore cyclical hair growth might depend on the ability of the dermal papilla to synthesize and release soluble growth and differentiation factors toward pre-existing capillaries. We characterized an angiogenic growth factor in the conditioned medium of dermal papilla cells indistinguishable from vascular endothelial growth factor as judged by biochemical and immunologic criteria. In addition, these cells bind vascular endothelial, growth factor on two binding sites and proliferate or migrate in the presence of this growth factor. Moreover, neutralizing antibodies inhibit these biologic effects, confirming that vascular endothelial growth factor might contribute to hair growth either by acting directly on papilla cells or by stimulating the local vascularization.

Keratitis, ichthyosis, and deafness (KID) syndrome. Vertical transmission and death from multiple squamous cell carcinomas.

A father and daughter had typical clinical features of the keratitis, ichthyosis, and deafness (KID) syndrome, as described by Skinner et al in 1981. To our knowledge, ours is the first observation of a vertical transmission of this syndrome. The mechanism of inheritance is uncertain. These two patients as well as the 26 previously described exhibited a typical hyperkeratotic eruption, which should not be confused with ichthyosis. The characteristic features are diffuse hyperkeratosis, keratotic plaques, reticulated hyperkeratosis on the face, peribuccal grooves, and heavy-grain leatherlike keratoderma. The occurrence of multiple squamous cell carcinomas underlines the seriousness of this congenital ectodermal defect. Etretinate can relieve the lesions without actually improving the chances of survival.

Titanium pigmentation. An electron probe microanalysis study.

A patient had an unusual pigmentary disease induced by titanium dioxide. The use of a topical cream containing titanium dioxide caused a xanthomalike appearance on the patient's penis. Electron probe microanalysis was valuable in establishing the cause of this balanitis.

Stage I cutaneous malignant melanoma: risk factors of loco-regional recurrence after wide local excision and clinical perspectives.

Two hundred and nineteen patients admitted to the Centre Claudius Regaud over a 14-year period for a stage I cutaneous malignant melanoma were retrospectively evaluated for loco-regional recurrence rates, risk factors and survival rates following wide primary excision. Five and 8 year survival rates corrected for deaths owing to concurrent illness were 77% and 73%. The loco-regional control rate was 69% (151/219). Distant metastases occurred in 59% (40/68) of patients who had a loco-regional recurrence, versus 11% (16/151) of patients when loco-regional control was obtained (P < 0.001). Multivariate analysis was used to ascertain which risk factors act independently as predictors of poor loco-regional control. Anatomical location of the primary ('head and neck-trunk-hands and feet' vs 'proximal limb') and thickness formed the best model in this respect among 11 prognostic factors studied. Since loco-regional recurrence may be associated with an increased risk of distant metastatic disease, we advocate the use of elective regional lymph node dissection in stage I patients at high risk of loco-regional recurrence in the hope that a portion of these patients may have increased survival owing to lack of development of widespread metastases.

Idiopathic pigmentation of the hands. Professional exogenous ochronosis? A new entity?

A case of ochronosis-like pigmentation of the hands is described. The following criteria were fulfilled: (1) presence of blue to black spots confined to the hands: (2) pitch-black macroscopic appearance of the biopsy specimen; (3) abundance of granular material in the whole connective structures on microscopic examination of an unstained specimen just mounted on a slide; (4) numerous pigmented granules in the elastic and collagen fibers: (5) no family history, abnormal coloration of the urine, taking of drugs, or rheumatism; (6) onset in a manual worker exposed to benzenic substances. This seems to be a new entity, probably a variant of exogenous ochronosis produced by professional contacts with some agents and perhaps a professional benzenic ochronosis.

Inhibitory effects of bFGF, VEGF and minoxidil on collagen synthesis by cultured hair dermal papilla cells.

Dermal papilla cells of rat vibrissa follicles cultivated in monolayers and in three-dimensional collagen gels show a different morphology in these culture systems. Dermal papilla cells cultured in lattices tend to express morphological features resembling those seen in vivo. Quantification of total collagen by incorporation of 3H-proline in monolayer cultures and in collagen lattices show that the amount of collagen found in dermal papilla cells is higher than that secreted. Moreover, collagen synthesis measured in lattices is reduced to about 50% of that found in monolayer cultures. The influence of growth factors on collagen synthesis by hair dermal papilla cells was investigated. We studied the effects of basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF) and minoxidil on collagen synthesis in monolayers and in lattices. VEGF, bFGF and minoxidil significantly decreased the total amount of collagen. In monolayer cultures, there was approximately a 30% inhibition of collagen production with 5 ng/ml bFGF, 0.1 ng/ml VEGF and 100 ng/ml minoxidil. However, in the lattices this inhibition was reduced to about half. These results suggest that both culture substrate and growth factors influence collagen production by rat hair dermal papilla cells.

Vitamin B-12 induced acnes.

A type of acne induced by vitamin B-12 deserves a special place among acneiform eruptions. The eruption is monomorphic and of a particular type. It consists of voluminous folliculitis lesions which develop acutely after the first injections of vitamin B-12 and disappear rapidly when treatment is discontinued. The etiologic and pathogenic mechanisms of the disease are not know.

[D-Penicillamine effect on collagen synthesis and structural maintenance Red Sirius staining with polarized-light examination. The value of this staining in cases of collagen diseases (author's transl)]. / Appréciation de l'effet de la D-Pénicillamine sur la synthèse et le maintien de la structure collagène, grâce à la coloration histologique par le Rouge Sirius examinée en lumière polarisée. Discussion de la valeur de cette coloration en pathologie du collagène.

A severe systemic sclerodermia has been treated by D-Penicillamine. A pathological study before and after treatment showed important changes of the collagen structure. The soluble or foetal collagen fraction is enhanced. By the Red-Sirius staining with polarized light examination of the bundles of foetal collagen are green and bright. Then, this staining appears as a marker of collagen structures.

[Drug hypersensitivity syndrome to valproic acid]. / Syndrome d'hypersensibilité médicamenteuse à l'acide valproïque.

BACKGROUND: Drug-induced hypersensitivity syndrome is an uncommon but potentially life-threatening idiosyncratic drug reaction. It is usually due to aromatic anti-convulsants. We report the second case induced by sodium valproate, a non-aromatic anticonvulsant. CASE REPORT: A 28-year-old woman was treated with sodium valproate for 5 weeks. She suddenly developed a generalized maculo-papulous eruption with fever, node enlargement, hypereosinophilia and altered liver function. DISCUSSION: Drug-induced hypersensitivity is rarely induced by valproic acid. The time-course and positive patch tests using the diluted drug establish the diagnosis.

[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).

[Pilar dysplasies studied in polarized light. An attempt to actualize nomenclature (author's transl)]. / Etude en lumière polarisée des dysplasies pilaires. Essai d'actualisation de la nomenclature.

The study of congenital hair defects can be made with many methods among which the examination of the hair shaft under polarized light is the most interesting. This scientific, precise and complete method bring the third dimension, allows one to see the slightest structural abnormalities of hair, to make a revision of the classical nomenclature, and should become the routine method for hair examination. We present the principles, the technique and the results.

[Syringomas mongolism, Marfan's disease and Ehlers-Danlos' disease]. / Syringomes, mongolisme, maladie de marfan et syndrome d'ehlers-danlos. Nouvelle entité posant les rapports des syringomes avec les maladies héréditaires du tissu conjonctif

The authors report a quite unusual case in which an eruption of syringomas, mongolism, Marfan's disease and Ehlers-Danlos' disease were associated. They emphasize the originality of the intricate appearance of syringomas on the ichthyosiform skin due to mongolism. They also stress the importance of the dysplasia of the connective tissue demonstrated by electron microscopy and the cause-effect relationships between the dysplasia of the connective tissue and the syringomas, the former accounting for the latter.

[Congenital atrichia with cysts]. / Atrichie congénitale avec kystes.

INTRODUCTION: Congenital atrichia with papular lesions is a rare congenital ectodermic dysplasia. CASE REPORT: A male child had atrichia of the scalp and eyebrows from birth. The atrichia was associated with epidermic cystic lesions of the scalp. Biopsy showed cystic piler follicles within the derma surrounded with an inflammatory infiltration of multinucleated giant cells. DISCUSSION: In most reported cases, scalp hair is present at birth and then falls within the first three months of life. Follicular cysts appear later. This syndrome generally occurs sporadically and the mode of inheritance is unknown.

[Atypical cutaneous mycobacterium diseases. Results of a national survey]. / Les mycobactérioses cutanées atypiques. Résultats d'une enquête nationale.

We report the results of a retrospective inquiry concerning atypical cutaneous mycobacterioses in France over the last 5 years. Ninety-two cases were observed, contracted from aquariums (50 p. 100), in swimming pools (4.4 p. 100) and as a result of mesotherapy (15.2 p. 100); 66.3 p. 100 of the patients had no other pathology; 17.4 p. 100 were immunodepressed. Bacteriological examination was positive in 44.7 p. 100 of the cases; swabbing, scratching and punturing were better than biopsy to obtain a bacteriological culture. Mycobacteria were identified in 59.8 p. 100 of the cultures. In order of frequency, the pathogens were Mycobacterium marinum (from aquariums), M. chelonae (from iatrogenic lesions) and M. avium-intracellulare (in immunodepression). M. fortuitum, M. ulcerans, M. flavescens, M. haemophilum and M. kansasii were rare. The formation of epithelial giant-cell granulomas was observed in patients without any other pathology. Non-specific infiltration was found in patients with immunodepression and bacteriological examination was often positive in those with non-specific infiltrates. The treatment of atypical cutaneous mycobacterioses is always difficult; third generation tetracyclines and antibacterial combinations are often prescribed, but the results of in vitro tests are not reproducible in vivo. New antibiotics, such as clarithromycin, quinolones, ansamycin and clofazimine, are currently being tested.

[Dietary carotenodermias]. / Caroténodermies diététiques.

Four cases of carotenodermia are presented, secondary to marked ingestion of carotenoid-rich vegetables. The first case was a 34 year old woman who presented with yellow palms and soles while on Weight Watchers diet. Loss of weight was accompanied by irregular menses. The second case was a 21 year old woman with orange palms and soles probably due to lycopenemia by tomatoes rich regimen. The third case is a 52 year old woman with the same type of diet as in case 1, associated with high cholesterol level. The fourth case is a 1.5 year old boy with a high intake of commercially available meals ("petits pots"). All the patients were free of disease usually associated with high level of carotenemia. Irregular menses or amenorrhea may be observed in such cases, either due to the rapid weight of loss, or as a manifestation of psychiatric disorder, and anorexia nervosa is possibly encountered. The toxicity of carotenoids is unproven and others substances ingested with high content vegetables diets are possible answerables.

[Tolerability of an aromatic retinoid (RO 10 9359, etretinate, Tigason, Roche). Research on its toxicity on hematopoietic, renal and thyroid functions. Interactions with the metabolism of natural retinoids]. / Tolérance du rétinoïde aromatique (RO 10 9359, étrétinate, Tigason, Roche). Recherche d'une toxicité sur les fonctions hématopoïétique, rénale et thyroïdienne. Interactions avec le métabolisme des rétinoïdes naturels.

59 patients with keratinisation diseases have been received RO 10 9359. There is a clinical medicum tolerance. Biologic controls have been carried out before and after a 3 month treatment. There is a good biological tolerance for the hematopoietic, glucidic, renal and thyroid functions. Thus the hepatic tolerance is poor for the patients with a predisposition for hepatic diseases (plethorics, alcoholics).