A gene for hypotrichosis simplex of the scalp maps to chromosome 6p21.3.

Hypotrichosis simplex of the scalp (HSS) is an autosomal dominant form of isolated alopecia causing almost complete loss of scalp hair, with onset in childhood. After exclusion of candidate regions previously associated with hair-loss disorders, we performed a genomewide linkage analysis in two Danish families and localized the gene to chromosome 6p21.3. This was confirmed in a Spanish family, with a total LOD score of 11.97 for marker D6S1701 in all families. The combined haplotype data identify a critical interval of 14.9 cM between markers D6S276 and D6S1607. Localization of the locus for HSS to 6p21.3 is a first step toward identification of the gene. The gene will give important insights into the molecular and cellular basis of hair growth on the scalp.

[Methotrexate and pregnancy]. / Methotrexat og graviditet.

A 39-year-old woman had a spontaneous abortion at the 13th-14th gestational week. Not knowing that she was pregnant, she had taken two doses of methotrexate of 15 mg for psoriasis--one dose at the conception time and one dose a week later. Autopsy of the foetus revealed no malformations. Guidelines for low-dose methotrexate treatment before and after conception are discussed.

Efficacy, tolerability, and safety of calcipotriol ointment in disorders of keratinization. Results of a randomized, double-blind, vehicle-controlled, right/left comparative study.

BACKGROUND AND DESIGN: Disorders of keratinization are a heterogeneous group of diseases that have in common a defect in cornification. The bioactive form of vitamin D3 has been shown to modulate epidermal proliferation and differentiation. The purpose of the present study was to determine the effect of the synthetic vitamin D3 calcipotriol in a randomized, double-blind, placebo-controlled, right/left comparative study. The 67 patients included in the study were at least 12 years of age and had the following diseases: ichthyosis vulgaris (n = 9), X-linked ichthyosis (n = 8), congenital ichthyosis (n = 10), hereditary palmoplantar keratoderma (n = 20), keratosis pilaris (n = 9), and Darier's disease (n = 11). Calcipotriol ointment (50 micrograms/g) and placebo (vehicle of calcipotriol ointment) were applied to all patients twice daily for up to 12 weeks. The patients were allowed to use up to 120 g of calcipotriol ointment per week. RESULTS: At the end of the treatment regimen, calcipotriol ointment had an effect on the improvement of the ichthyoses, although to a variable degree. No therapeutic effect was detected in palmoplantar keratoderma or keratosis pilaris. Eight of 12 patients with Darier's disease had to be withdrawn because of skin irritation or a worsening of the disease. Skin irritation occurred in 18 cases (26%) only on the calcipotriol-treated side, and in one case (1%) only on the placebo-treated side. Nine cases (13%) had irritation on both sides. The amount of calcipotriol ointment used per week was lowest in palmoplantar keratoderma (mean, 11.8 g/wk; range, 2.1 to 25.6 g/wk) and highest in congenital ichthyosis (mean, 59.3 g/wk; range, 11.4 to 94.7 g/wk). There was no clinically significant change of serum calcium levels during the treatment period. CONCLUSION: Short-term treatment with calcipotriol ointment (50 micrograms/g) used in amounts up to about 100 g/wk is moderately efficacious, well-tolerated, and safe in adult patients with various ichthyoses.

Correction of steroid sulfatase deficiency by gene transfer into basal cells of tissue-cultured epidermis from patients with recessive X-linked ichthyosis.

To develop an experimental model for somatic gene therapy we have tried to correct the steroid sulfatase (STS) deficiency in tissue-cultured primary epidermal keratinocytes from patients suffering from recessive X-linked ichthyosis. An efficient Epstein-Barr virus-based vector was constructed, in which full-length steroid sulfatase cDNA is located between an SV40 early promotor and processing signals. After STS gene transfer into cultured basal cells from ichthyotic skin, the cells produce large amounts of enzymatically active steroid sulfatase protein. The subpopulation of transfected cells can be made to produce approximately 100 times more STS activity than normal keratinocytes. Keratinocytes from patients suffering from recessive X-linked ichthyosis display an abnormal phenotype when developing a multilayered tissue in culture: Initially an extensive burst of keratinization is observed, followed by rapid, premature shedding and degradation of most suprabasal cell layers, leaving a culture with hyperproliferative relatively immature keratinocytes. Transfection of these immature ichthyotic cells with the functional STS construct led to an increase in the amount of retained cell material in the culture medium, indicating an increased cell maturation. It is possible to genetically label individual transfected epidermal cells with a reporter gene. Cotransfection experiments with STS and reporter gene vectors show that the cohort of transfected cells had a tendency to develop less rapidly since they became overrepresented in the smaller size classes at the same time the total population was somewhat shifted toward higher cell sizes. We interpret these results as an indication that restoration of the enzymatic activity induces a more normal maturation of the transfected keratinocytes.

Tinea corporis due to Trichophyton verrucosum in recessive, X-linked ichthyosis.

An 18-year-old male agricultural worker with recessive X-linked ichthyosis was found to have ringworm infection with Trichophyton verrucosum, which resulted in well-demarcated clearing of the ichthyotic scaling in affected areas. However, rapid recurrence of the abnormal cornification was observed after treatment of the fungal infection. Some possible mechanisms regarding the effect of fungi on hyperkeratinization are discussed.

[Cholesterol microemboli]. / Kolesterolmikroembolier.

Cholesterol microemboli are caused by cholesterol crystals released from arteriosclerotic plaques in the major arteries. The clinical picture is illustrated by two case histories with symptoms in the form of myalgia, livedo reticularis and gangrene. The diagnoses were verified by demonstration of cholesterol crystals in the affected tissue. The pathogenesis is illustrated and, on the basis of the literature, it is emphasized that cholesterol microemboli are probably often overlooked clinically and that an increasing incidence must be anticipated on account of the increasing frequency of invasive procedures and treatments of arteriosclerotic vascular disease.

Familial hypotrichosis of the scalp. Autosomal dominant inheritance in four generations.

We describe a Danish family of four generations suffering from hypotrichosis of the scalp. Age at onset was 6-17 years and almost total scalp alopecia was reached by the age of 14-21 years. No associated ectodermal defects were present. Nine of 22 persons covering four generations were affected. Growth of the scalp hair slowly decreased and was accompanied by a gradual, diffuse hair loss without regional variation. A scalp biopsy was performed, revealing a non-scarring alopecia with features of androgenetic alopecia. The pedigree was compatible with autosomal dominant inheritance.

Occurrence of Ureaplasma urealyticus and Mycoplasma hominis in non-gonococcal urethritis before and after treatment in a double-blind trial of ofloxacin versus erythromycin.

The efficacy of ofloxacin, a new quinolone derivate, was tested against that of erythromycin in a prospective double-blind trial in patients with non-gonococcal urethritis (NGU) with special reference to the occurrence of Mycoplasma hominis and Ureaplasma urealyticum. 188 male NGU patients were randomized to treatment with either ofloxacin 200 mg b.i.d. or erythromycin 500 mg b.i.d. for seven days. Before treatment eight (4.3%) patients, five in the erythromycin group and three in the ofloxacin group, were M. hominis positive. At follow-up day 8 and 15 after start of treatment all five in the erythromycin group and two in the ofloxacin group were still positive. U. urealyticum was recovered in 16 patients (8.5%) before treatment. One patient was still positive in the erythromycin group when examined day 15, whereas all patients were negative in the ofloxacin group at both follow-up controls. Clinically, the efficacy of treatment day 15 was 77.4% in the erythromycin group and 84.3% in the ofloxacin group. The difference was not significant. Side-effects occurred in 38.5% in the erythromycin group and in 21.3% in the ofloxacin group. This difference is significant. Ofloxacin is effective in the treatment of NGU in males and is an alternative to conventional antibiotic treatment.

Psoriasis and polyneuropathy. Three case histories.

Neurophysiological examination of 3 psoriasis patients with symptoms of polyneuropathy revealed varying degrees of both sensory and motor nerve affection and indicated nerve fibre loss as well as demyelination. Previous reports have suggested a connection between peripheral nerves and psoriasis.

[Epididymitis caused by amiodarone]. / Amiodaron-induceret epididymitis.

A case of epididymitis developed in a 33 year old man after treatment with the anti-arrhythmic agent, amiodarone, for approximately 18 months. No signs of bacterial infection or anatomical abnormalities were found. Amiodarone as the cause of epididymitis has only previously been described on a few occasions. We stress the importance of considering this adverse effect of amiodarone therapy as a differential diagnosis in the etiology of epididymitis.

Epididymitis caused by treatment with amiodarone.

Epididymitis is described in a man aged 33 who had been treated with the antiarrhythmic agent, amiodarone. No signs of bacterial infection or anatomical abnormalities were found. Amiodarone as the cause of non-infectious epididymitis has been reported. This additional case stresses the importance of considering an adverse effect of amiodarone treatment as a cause when making a differential diagnosis of epididymitis.

Treatment of nongonococcal urethritis: comparison of ofloxacin and erythromycin.

Ofloxacin, a new quinolone carboxylic acid derivative, has been reported to be effective and safe in the treatment of nongonococcal urethritis (NGU). In the present investigation 188 male outpatients with NGU were randomized to double-blind treatment with either erythromycin (500 mg twice a day) or ofloxacin (200 mg twice a day) for seven days. Before therapy Chlamydia trachomatis was isolated from 43.6% of the patients. One relapse and one reinfection occurred in the erythromycin-treated group, whereas all patients in the group given ofloxacin were culture-negative at follow-up. Among the C. trachomatis-positive group of patients, the clinical efficacy of ofloxacin was 83.7%, and that of erythromycin, 77.4% at the final follow-up. In the C. trachomatis-negative group, the efficacy of ofloxacin was 93%, and that of erythromycin, 84.3%. The differences are not significant. No serious adverse effects were demonstrated. The results indicate that ofloxacin might be a valuable alternative for the treatment of NGU in men.

Lipoprotein electrophoresis in recessive X-linked ichthyosis.

Recessive X-linked ichthyosis (RXLI) is consistently associated with steroid sulphatase deficiency, and a definite diagnosis can be made by measurement of the activity of this enzyme, e.g. in cultured skin fibroblasts and leucocytes. Demonstrating an increased electrophoretic mobility of plasma low-density lipoprotein in RXLI patients has been proposed as a simpler method for the diagnosis of this condition. Our findings in 7 RXLI patients and 7 normal controls confirmed that a discrimination between patients and controls can be obtained by routine lipoprotein electrophoresis. However, due to variation in the results of repetitive performances further studies are needed to evaluate the overall reliability of this diagnostic approach.