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Biomedical subjects

Rudolf Happle

Publications and source records attributed to Rudolf Happle.

At least 55 records · Page 3Linked to original sources
PubMed2003

Whorled scarring alopecia: a rare phenomenon in incontinentia pigmenti?

Incontinentia pigmenti is a rare X-linked dominant disease that affects the ectodermal tissues and is usually lethal in males. Two girls, 1 Malay and 1 Chinese, with incontinentia pigmenti of the Bloch-Sulzberger type had a whorled pattern of scarring alopecia. This phenomenon, hitherto unreported in association with this disorder, corresponded to the lines of Blaschko. The mother and maternal grandmother of the Malay girl also had whorled scarring alopecia. This phenomenon is permanent and can be used as a marker to ascertain affected adult women who may no longer have cutaneous manifestations. X chromosome inactivation in females during early embryogenesis results in a mosaic population of cells, which explains the linear and patchy cutaneous manifestations of incontinentia pigmenti.

Alopecia Areata↗
PubMed2003

Alopecia areata: treatment of today and tomorrow.

It is the aim of this article to review and appraise available data on treatments for alopecia areata (AA) according to the demands of evidence based medicine. Studies evaluating the efficacy of a treatment for AA should include appropriate controls, use cosmetically acceptable hair regrowth as a parameter for treatment success, include patients with AA totalis, universalis or extensive patchy AA, and exclude patients suffering from AA for less than 3 months. Moreover, the treatment must be safe over a prolonged period of time. Among the various therapeutic approaches presently available for AA, only treatment with contact sensitizers such as diphenylcyclopropenone or squaric acid dibutylester has been shown to be effective in studies that fulfill these criteria. Improved future treatments may be immunosuppressive or immunomodulatory targeting of the autoimmune pathogenesis of AA, or they may otherwise protect hair follicles from the injurious effects of inflammation. Such possible future therapeutic approaches include the incorporation of immunomodulatory agents into liposomes as an improved vehicle; inhibition of apoptosis mediated by the Fas-FasL system; inhibition of the lymphocyte homing receptor CD44v10; induction of tolerance.

Adjuvants, Immunologic↗
PubMed2003

Morphological approach to hair disorders.

The Workshop on the morphological approach to hair disorders brought together a group of clinicians involved in hair biology research. Six speakers spoke on a range of topics that can be grouped broadly into a central theme. It summarizes the evolution of medical research. The section by Tosti and coworkers describes a patient with a new unique syndrome. The section by Ferrando and colleagues provides a framework in which patients with rare hair disorders can be classified. The section by Whiting tries to define the normal anatomy of the hair follicle and both horizontal and vertical sections. It is only when normal anatomy has been absolutely defined that pathological deviations can be recognized. The section by Sinclair and coworkers attempts to estimate the reliability of histological diagnosis so that its true value of pathology can be recognized. The section by Zlotogorski and coworkers shows how accurate clinical and histological definition of disease acts as the cornerstone for gene discovery techniques. Once a causative mutation is found and a gene product identified, then the biological consequences of the altered protein product can be studied and the impact of the abnormal molecular function on hair biology can be understood. It is hoped that improved understanding of hair disease will then lead to useful therapeutic interventions. The final section by Leroy and Van Neste highlights the difficulties of evaluating therapeutic interventions in hair loss disease and proposes a new technique.

Alopecia↗
PubMed2003

Fas-deficient C3.MRL-Tnfrsf6(lpr) mice and Fas ligand-deficient C3H/HeJ-Tnfsf6(gld) mice are relatively resistant to the induction of alopecia areata by grafting of alopecia areata-affected skin from C3H/HeJ mice.

Alopecia areata is suspected to be a T cell-mediated autoimmune disease of the hair follicle, where Fas is expressed on hair follicles and Fas ligand on perifollicular infiltrates. To elucidate whether the Fas/Fas ligand pathway is of pathogenetic significance in alopecia areata, we investigated whether alopecia areata can be induced in Fas-deficient and Fas ligand-deficient mice and whether alopecia areata develops in Fas-deficient and Fas ligand-deficient skin. Therefore, we induced alopecia areata by grafting alopecia areata-affected C3H/HeJ mouse skin on to C3H/HeJ mice (control), on to Fas ligand-deficient C3H/HeJ-Tnfsf6(gld) mice or Fas-deficient C3.MRL-Tnfrsf6(lpr) mice. All control mice developed alopecia areata, whereas no Fas-deficient mice showed hair loss and two of seven Fas ligand-deficient mice developed only transitory, limited alopecia areata. Moreover, skin from C3H/HeJ mice (control), C3H/HeJ-Tnfsf6(gld) mice, and C3.MRL-Tnfrsf6(lpr) mice was grafted on to C3H/HeJ mice with extensive alopecia areata. Skin grafts from control mice developed hair loss, whereas Fas-deficient and Fas ligand-deficient skin grafts were spared from alopecia areata. Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling and immunofluorescence studies revealed an increased number of apoptotic cells and expression of Fas on hair follicles as well as expression of Fas ligand on cells of the perifollicular infiltrate in C3H/HeJ mice with alopecia areata, whereas in Fas-deficient and Fas ligand-deficient mice apoptotic cells were virtually absent in hair follicles. The results suggest that the Fas/Fas ligand pathway plays an important pathogenetic role in alopecia areata.

Alopecia Areata↗
PubMed2003

Linear atrophoderma of Moulin: postulation of mosaicism for a predisposing gene.

Hyperpigmented atrophoderma arranged in a pattern following the lines of Blaschko and appearing during childhood or adolescence on the trunk or the limbs is a characteristic feature of linear atrophoderma of Moulin. We review 15 published reports and describe 4 additional cases. Histopathologically, there is no clear sign of atrophy found in specimens examined by light microscopy. It might well be argued that a focal reduction of subcutaneous fatty tissue contributes to the obvious clinical atrophy. The cause and pathogenesis of the disorder remains unknown. It may reflect mosaicism caused by a postzygotic mutation that occurred at an early developmental stage, in analogy to many other diseases distributed along Blaschko's lines. Linear atrophoderma of Moulin may reflect the action of an autosomal lethal gene surviving by mosaicism. There are so far no reports of a familial occurrence that could favor a paradominant transmission of linear atrophoderma of Moulin. However, theoretically, the postzygotic mutation giving rise to an aberrant cell clone could still be nonlethal. In a heterozygous individual, a postzygotic mutational event might lead to loss of the corresponding wild-type allele at the atrophoderma locus. This would give rise to a homozygous cell clone, which becomes manifest along the lines of Blaschko later in life.

Adolescent↗
PubMed2003

Allergy and irritation: an adverse association in patients with atopic eczema.

The pathomechanism of atopic eczema is complex. Two of the most important exogenous factors for atopic eczema are allergenic and irritant substances. In this study we investigate the combined effect of topical aeroallergens and irritation on the skin of atopic individuals. We performed patch testing with several aeroallergens (atopy patch test) and with an irritant, sodium lauryl sulphate, on clinically unaffected skin of 30 sensitized patients with atopic eczema. Application was conducted alone and as a consecutive application. Healthy volunteers served as controls. Evaluation was made by measurement of transepidermal water loss 2 h after removal of the patches. In atopic patients, we found increased levels of transepidermal water loss induced by the aeroallergens as well as by sodium lauryl sulphate. The most impressive barrier disruption was seen after application of house dust mite, followed by cat dander and grass pollen. However, the consecutive application of aeroallergens and sodium lauryl sulphate led to a highly pronounced increase in transepidermal water loss. Hence, in sensitized atopic subjects the combined effect of aeroallergens and detergents may cause severe skin problems, and this may be relevant in daily practice.

Adolescent↗
PubMed2003

Influence of climatic conditions on the irritant patch test with sodium lauryl sulphate.

Irritant patch testing with detergents is increasingly being used as a measure of skin barrier function, but there is evidence that climatic changes can influence the test outcome. In this study we investigated the relation between cutaneous reactivity to a detergent and climatic conditions. Between January 2000 and December 2001 epicutaneous patch testing with 0.5% sodium lauryl sulphate was performed on the forearm of 487 volunteers and evaluated by measuring transepidermal water loss (TEWL). Atopic individuals were excluded. Climatic conditions recorded by the German Meteorological Service were then compared with the test outcome. Climatic measurements 7 days before evaluation of the patch test were used to calculate an arbitrary mean value for each climatic parameter. A strong correlation was observed between temperature, steam pressure, absolute and relative humidity and the increase in TEWL, and most pronounced during winter and spring. The data provide experimental confirmation of epidemiological studies in which the incidence of irritant skin changes was found to be increased during the winter season with cold and dry air. For the first time, two formulae for adjusting TEWL values according to climatic conditions are presented. It is possible with these formulae to compare between a measured TEWL value and a calculated value.

Adolescent↗
PubMed2002

Pigmentary mosaicism of the hyperpigmented type in two half-brothers.

Pigmentary mosaicism is a heterogeneous cutaneous phenotype that is often associated with extracutaneous anomalies. It is widely accepted that these phenotypes arise de novo as a result of a postzygotic mutation, leading to a mosaic status of the embryo. In the vast majority of cases, the occurrence of pigmentary mosaicism is sporadic. We report two paternal half-brothers affected with pigmentary mosaicism of the hyperpigmented type. The hyperpigmentation in both patients is distributed along the lines of Blaschko. In addition, mental retardation, facial asymmetry, short stature, scoliosis, and short fingers with clinodactyly of the 5th digit were noted in one of them. Chromosome analysis in this 15-year-old patient demonstrated a mosaic 46,XY,dup(3)(p21.3;pter)/46,XY with 12% aberrant cells in lymphocytes and 2% in skin fibroblasts derived from a hyperpigmented area. His nine-year-old half-brother had similar systematized hyperpigmented skin lesions, macrocephaly, facial asymmetry, and clinodactyly of the 5th digit. Chromosome analysis of peripheral lymphocytes showed a normal karyotype 46,XY. A skin biopsy could not be obtained. So far, some familial cases of hypopigmentation along the lines of Blaschko have been reported, but familial occurrence of the hyperpigmented type of pigmentary mosaicism appears to be extremely unusual. It is difficult to establish a causal relationship with the chromosomal mosaicism as observed in patient 1. Paradominant transmission seems unlikely because this would likewise imply that the chromosomal mosaicism is an incidental finding.

Adolescent↗
PubMed2002

A novel missense mutation of NSDHL in an unusual case of CHILD syndrome showing bilateral, almost symmetric involvement.

The CHILD syndrome (MIM 308050), an acronym for congenital hemidysplasia with ichthyosiform nevus and limb defects, is an X-linked dominant trait with lethality for male embryos. Recently, we elucidated the underlying gene defect by demonstrating point mutations in NSDHL (NAD[P]H steroid dehydrogenase-like protein) at Xq28 in 6 patients with classic CHILD syndrome. The most striking clinical feature is an inflammatory nevus that usually shows a unique lateralization with strict midline demarcation. Ipsilateral defects involve all skeletal structures and internal organs such as the brain, the lung, the heart, or the kidney. As an exception to this rule, in some cases the CHILD nevus may occur in a more or less bilateral distribution. In 1997 Fink-Puches et al described a case of CHILD nevus with an almost symmetric arrangement. To test the correctness of the diagnosis, we now examined blood lymphocytes of this patient by single-strand conformation analysis and genomic sequencing. We identified a novel missense mutation in NSDHL that potentially may impair protein function. We conclude that a diagnosis of CHILD syndrome can be based on clinical features such as the highly characteristic morphology of the CHILD nevus. A symmetric distribution of this nevus can exceptionally be seen in patients with CHILD syndrome, and this bilateral involvement should not mislead the clinician to any other diagnosis. Apparently, the effect of random X-inactivation is responsible for different patterns of cutaneous involvement in female carriers of NSDHL mutations.

3-Hydroxysteroid Dehydrogenases↗
PubMed2002

Multiple eruptive dermatofibromas: a review of the literature.

In this review we summarize the characteristic features of multiple eruptive dermatofibromas based on an analysis of cases in the literature. Many researchers have reported multiple eruptive dermatofibromas diagnosed using the definition of "multiple" as the presence of at least 15 lesions. However, this criterion is arbitrarily chosen and might not be entirely valid for all cases. A more precise definition may include the eruption of several multiple eruptive dermatofibromas reported within a short period of time. Because more than half of the patients with multiple eruptive dermatofibromas have underlying diseases, and more than 80% of the underlying diseases are immune-mediated, multiple eruptive dermatofibromas could possiblv be considered as a partial manifestation of an immune-mediated disease. This underscores the possibility of early diagnosis of immune-mediated diseases in patients with multiple eruptive dermatofibromas.

Adolescent↗
PubMed2002

Dohi Memorial Lecture. New aspects of cutaneous mosaicism.

The concept of cutaneous mosaicism has today been proven at the cellular level in at least fifteen different skin disorders. We can distinguish five different patterns of mosaicism, including the phylloid pattern and the lateralization pattern. Etiologically, cutaneous mosaics can be divided into two large categories, epigenetic mosaicism and genomic mosaicism. All forms of epigenetic mosaicism known so far, including the various patterns of X-inactivation, appear to be caused by the action of retrotransposons. A new concept is functional autosomal mosaicism transmittable through the action of retrotransposons, which has been described in mice and dogs and may explain, for example, the familial occurrence of pigmentary mosaicism along the Blaschko lines in human skin. Among the examples of mosaicism of autosomal lethal mutations, phylloid hypomelanosis is a recently recognized neurocutaneous entity caused by mosaic trisomy 13. Possible examples of a type 2 segmental manifestation now include at least fifteen different autosomally dominant skin disorders. This phenomenon is most frequently found in glomangiomatosis, cutaneous leiomyomatosis, and disseminated superficial actinic porokeratosis. Recently proposed examples of didymosis (twin spotting) include cutis tricolor, paired patches of excessive or absent involvement in Darier disease, and didymosis aplasticosebacea characterized by coexistent aplasia cutis congenita and nevus sebaceus. To the list of possible examples of paradominant inheritance, cutis marmorata telangiectatica congenita and speckled lentiginous nevus syndrome have now been added. Revertant mosaicism giving rise to unaffected skin areas in autosomally recessive cutaneous traits will certainly likewise be recognized more often when clinicians are bearing this concept in mind. Such cases can be taken as examples of "natural gene therapy".

Adolescent↗