Biomedical subjects
Publications and source records attributed to R Happle.
Cutis marmorata teleangiectatica congenita is a rare birth defect of unknown etiology. The disease is characterized by reticular teleangiectasias and phlebectasias. Among the associated anomalies, hypoplasia of an affected extremity is most frequently observed. On the basis of two cases, the clinical features of cutis marmorata teleangiectatica congenita are described and the differential diagnosis discussed.
Inflammatory linear verrucous epidermal nevus (ILVEN) is a rare skin disease with characteristic clinical and histological changes. The approximately 100 cases so far reported include only one familial occurrence involving a woman and her nephew. We report the occurrence of typical ILVEN in a 47-year-old mother and her 17-year-old daughter. So far, no clear-cut genetic interpretation of this observation can be given. Apart from coincidence, various genetic explanations are considered, including X-linked inheritance with extreme lyonization.
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Lymphocyte proliferation and nucleoid sedimentation were studied in a patient with premature aging resembling the Werner's syndrome (WS). Onset of patchy brown hyperpigmentations at the age of 9 months permitted distinction from classical WS and suggested a WS-like premature aging disease. By photometric recording of density changes during cell culture, we examined the course of cell proliferation after PHA stimulation over 7 days and compared these results to those obtained in two normal controls. Cultured cells of the patient displayed an aberrant proliferation pattern characterized by continuous growth without an initial reduction phase. The markedly reduced proliferative capacity of purified cells from the patient could in part be corrected by fetal bovine serum. The cells of the patient displayed a characteristic nucleoid sedimentation profile after ultraviolet irradiation indicating retarded DNA replication, which may be a common feature of various premature aging diseases. The absence of thermolability of cell proliferation and the presence of a high number of chromatid aberrations disclosed differences from classical WS.
It has previously been shown that, in patients with untreated progressive alopecia areata (AA), the peribulbar T4/T8 ratio is about 4:1. In the present study, the immunohistochemical findings obtained in untreated AA patients were compared to those obtained in patients who had received topical immunotherapy with diphencyprone. The untreated group consisted of 5 patients with progressive AA and 5 patients with inactive AA. The treated group consisted of 5 patients with a good response to diphencyprone and 5 patients with little or no hair regrowth after treatment. In untreated patients with progressive AA, the mean peribulbar T4/T8 ratio was 4:1, whereas in untreated patients with stable AA, the ratio was 2:1. In the treated patients with a good response to diphencyprone, the mean T4/T8 ratio was 1:1, while in the patients with poor or no response to treatment, the ratio was 0.7. In conclusion, topical immunotherapy considerably alters the peribulbar T4/T8 ratio in AA. The results are consistent with, but do not prove, the concept of topical immunomodulation.
We report the second family of ichthyosis bullosa, an entity that was first described by Siemens in 1937 and since then has fallen into oblivion. Clinically, ichthyosis bullosa is characterized by blistering resembling epidermolysis bullosa simplex and by generalized, yet circumscribed dark gray hyperkeratoses covering mainly the arms and the legs. Lichenification and superficially denuded areas (mauserung) are further prominent features. Histology disclosed intracorneal blister formation corresponding to the mauserung phenomenon and epidermolytic hyperkeratosis that was confined to the granular layer and to the uppermost layers of the prickle cells. On electron microscopic examination the keratinocytes of these layers displayed structural alterations of tonofilaments as usually observed in epidermolytic hyperkeratosis. Thus ichthyosis bullosa shares with bullous ichthyosiform erythroderma blistering and epidermolytic hyperkeratosis, but can be distinguished from this wellknown disease by the lack of erythroderma, by the mauserung phenomenon, by the confinement of acanthokeratolysis to the superficial layers of the epidermis, and by intracorneal blistering.
In the McCune-Albright syndrome, fibrous dysplasia of bones and various forms of endocrine dysfunction are associated with multiple pigmented skin lesions. Examination of a 4-year-old female patient and comparison with photographs published in the literature revealed that the cutaneous pigmentation is arranged in a systematized pattern following the lines of Blaschko. Apparently, this pattern visualizes the dorso-ventral outgrowth of two different populations of cells during early embryogenesis. As all cases of the syndrome are sporadic, it is postulated that the disease is caused by an autosomal "dominant" lethal gene, leading to loss of the zygote in utero. Cells bearing the mutation can only survive when they are intermingled with normal cells. The mosaic may arise either from a gametic half chromatid mutation, or from an early somatic mutation. This concept offers an explanation for the scattered asymmetric distribution of bone lesions, and for the observation that the endocrinopathy may be either of central or peripheral origin, according to the random distribution of the mutant population of cells.
We studied the hair of a 10-month-old girl who was suffering from acrodermatitis enteropathica, using light and polarizing microscopy before and after institution of zinc therapy. The hair was very thin and brittle. On light microscopy the shafts showed uneven diameter and some displayed atypical trichorrhexis nodosa with stretched fractures. Ten percent of the hair fibers exhibited nodal swellings of the pseudomonilethrix type. Polarization microscopy disclosed in 70% of all hair shafts an irregular pattern of alternating dark and bright bands. This anomaly was still present in 10% of the hair shafts after one and one-half years of zinc therapy, but could no longer be detected after two years of zinc supplementation. Repeated determinations of hair probes before and after treatment gave a low cystine content, however, being still in the normal range. We assume that the observed changes and the low hair cystine content can be attributed to the underlying zinc deficiency.
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We describe four patients with a combined vascular nevus, consisting of telangiectatic and angiospastic parts, and give a review of 28 observations previously reported. In all of these cases the two different nevoid skin changes are situated directly adjacent to each. Therefore we consider this combination not to be an incidental finding but to represent a distinct entity. For this anomaly, we propose the designation "nevus vascularis mixtus".
The lines of Blaschko represent a nonrandom developmental pattern of the skin fundamentally differing from the system of dermatomes. Many nevoid skin lesions display an arrangement following these lines. This is a review of case reports providing photographically documented evidence that the lines of Blaschko become manifest in the heterozygous state of various X-linked gene defects such as incontinentia pigmenti, focal dermal hypoplasia, X-linked dominant chondrodysplasia punctata, X-linked hypohidrotic ectodermal dysplasia, and Menkes syndrome. Hence, a causal relationship between lyonization and the lines of Blaschko seems quite obvious. Although it should be borne in mind that other genetic mechanisms such as somatic mutations or chimerism may give rise to the same linear pattern, the datable embryologic event of X-inactivation seems most suitable to explain the origin and nature of the lines of Blaschko. Apparently, in women affected with X-linked skin disorders the lines of Blaschko visualize the clonal proliferation of two functionally different populations of cells during early embryogenesis of the skin. The typical dorsal V-shape and the abdominal S-figure of these lines may result from an interference of the transversal coherent proliferation with the longitudinal growth and flexion of the embryo. In contrast to Blaschko's original assumption, it is now clear that these lines are independent from the metameric structure of the human body. Obviously, they represent a marker of the normal development of human skin. Therefore, a thorough study of the distribution pattern of X-linked skin disorders in women may give us a better insight into the early embryogeny of the human integument.
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Recently, autosomal-dominant lamellar ichthyosis (ADLI) has been shown to be a new genetic trait with clinical and histologic features similar to those of autosomal-recessive lamellar ichthyosis. In two patients affected with ADLI, the malpighian keratinocytes showed ultrastructural signs of increased cellular metabolism. The tonofilaments and keratohyaline granules were regular in structure and number. However, as a distinctive ultrastructural feature, a prominent transforming zone was found between the granular and horny layers. Moreover, a normal keratin pattern and only a limited number of lipid inclusions were observed in the stratum corneum. Thus, ADLI can be distinguished from the autosomal-recessive forms of lamellar ichthyosis, permitting a correct diagnosis when genetic counselling has to be given in sporadic cases.
Keratinization defects can be very severe and disfiguring diseases. The development of retinoids such as etretinate has provided us with an effective symptomatic form of oral therapy for these skin conditions. Based on our own experience, we briefly outline the therapeutic potential of etretinate in various keratinization defects (lamellar ichthyosis, Netherton syndrome, Sjögren-Larsson syndrome, mal de Meleda and juvenile pityriasis rubra pilaris). The toxicology of etretinate is reviewed with special regard to the treatment of children. Bone changes such as premature closure of the growth line or other unacceptable side-effects have so far not been observed. Guidelines for patient selection and for the safe treatment of children are given.
For the detection of the carrier state of X-linked hypohidrotic ectodermal dysplasia, sweat pore counts on fingertips or palms have been used in the past. The results obtained, however, were sometimes difficult to interpret. We here describe a more reliable method, using the entire back as a test area. We provide evidence that the distribution of sweat pores in carriers is not simply patchy. In four heterozygous women we were able to demonstrate a linear distribution of hypohidrotic areas. This pattern followed the lines of Blaschko, forming a typical V-shape over the spine. Apparently, these lines reflect the dorsoventral outgrowth of two functionally different populations of cells during early embryogenesis.
We report three cases of the Gianotti-Crosti syndrome (papulovesicular-acro-located syndrome of childhood), a self-limited common disease of childhood, which may be caused by various viral infections. The hepatitis B virus, however, is excluded by definition as a causal agent. The syndrome is characterized by itching papulo-vesicular skin lesions measuring 1-5 mm in diameter and localized to the limbs and face. The clinical and terminological differences between the HBsAG negative Gianotti-Crosti syndrome and the HBsAG positive Gianotti disease are emphasized.
The Papillon-Lefèvre syndrome is an autosomal recessive gene defect characterized by transgredient palmoplantar hyperkeratosis and periodontopathia leading to loss of the teeth. The syndrome is described in a 28-year-old man who had lost all of his teeth at the age of 10 years. Treatment with etretinate resulted in a marked improvement of the palmar and plantar skin lesions.
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