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Biomedical subjects

R Happle

Publications and source records attributed to R Happle.

At least 91 records · Page 5Linked to original sources
PubMed1999

[Pathogenetic significance of 5-alpha reductase isoenzymes for androgenetic alopecia].

Androgenetic alopecia is the most common form of hair loss in men and women. Although clinically different, the pathogenetic pathways leading to this type of hair loss are similar in both sexes. Recent experimental data enable us to explain some pathogenetic steps suggesting a pivotal role of type 2 5 alpha-reductase in the pathogenesis of androgenetic hair loss. In this review our current knowledge about the pathophysiology and treatment options of androgenetic alopecia is summarized.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed1999

[Patch testing with sodium lauryl sulfate: benefits and drawbacks in research and practice].

Patch testing with sodium lauryl sulfate (SLS) has been frequently used in the last decade. The evaluation of the SLS test can be performed visually, or with bioengineering methods. Among these, the transepidermal water loss is the most appropriate method, but measurements by laser Doppler flowmetry, colorimetry or corneometry may yield additional relevant data. Various factors such as age, area of testing or climatic conditions may also influence the SLS test, so such factors should be considered when different studies are compared. If correctly used, the SLS test can provide valuable information regarding the skin susceptibility to irritation. An overestimation of the test, just based on objective measurements with bioengineering methods, should be avoided, as the bioengineering data are capable of great precision and reproducibility, but can only define phenomena and not the causal event.

Dermatitis, Irritant↗
PubMed1999

Loss of heterozygosity in human skin.

Loss of heterozygosity (LOH) is a genetic mechanism by which a heterozygous somatic cell becomes either homozygous or hemizygous because the corresponding wild-type allele is lost. LOH has today been recognized as a major cause of malignant growth. This article gives a comprehensive review of skin disorders in which an origin from LOH has been either documented at the molecular level or postulated on the basis of clinical evidence. LOH has been shown to cause basal cell carcinoma, squamous cell carcinoma, and malignant melanoma, but this mechanism can likewise be taken as an important model to explain the origin of many other skin diseases such as benign hamartomas; type 2 segmental manifestation of autosomal dominant skin disorders; a pronounced segmental manifestation of acquired skin disorders with a polygenic background, superimposed on symmetric lesions of the usual type; paired mutant patches in the form of either allelic or nonallelic twin spotting; and the exceptional familial occurrence of some nevi, reflecting paradominant transmission. completion of this learning activity, readers should be familiar with the mechanism of LOH and its general significance for the biology of plants, animals, and humans. Participants should understand that this mechanism plays a crucial role not only in cutaneous malignant growth but also in the development of benign skin disorders, and they should be able to examine such diseases with a prepared mind to gain a better understanding of their origin.

Animals↗
PubMed1999

Three different autoimmune bullous diseases in one family: is there a common genetic base?

We report an unusual familial occurrence of autoimmune bullous diseases. Three members of a family suffered from three different autoimmune bullous diseases: pemphigus vulgaris (PV), linear IgA disease (LAD) and cicatricial pemphigoid (CP). The HLA type was determined in five family members: all were positive for HLA-DQ5/DR6, which is reported to be associated with susceptibility to PV. The CP patient was DQ7(3) positive, which is in concordance with enhanced susceptibility to ocular CP and CP. The LAD patient was B8 and DR3 negative but positive for HLA-A1. Our study supports the hypothesis that there is a genetically transmitted susceptibility to autoimmune bullous diseases but that additional factors seem necessary actually to develop a particular disease.

Adult↗
PubMed1999

Successful treatment of alopecia areata-like hair loss with the contact sensitizer squaric acid dibutylester (SADBE) in C3H/HeJ mice.

A type of hair loss closely resembling human alopecia areata has been described in C3H/HeJ mice. In order to test the assumed analogy with human alopecia areata, we investigated the efficacy of treatment with the contact allergen squaric acid dibutylester. In 12 C3H/HeJ mice with alopecia areata an allergic contact dermatitis was induced and elicited weekly on one side of the back by topical applications of squaric acid dibutylester. Overt hair regrowth was observed only on the treated side of the back in nine of 12 mice. Histopathologic examination revealed a change in the distribution of the inflammatory infiltrate from a dense perifollicular lymphocytic infiltrate around the mid and lower regions of hair follicles in untreated skin to a uniform presence in the upper dermis in treated skin. Immunohistomorphometric studies revealed that treatment with squaric acid dibutylester increased the CD4+/CD8+ ratio from approximately 1:2 in untreated alopecia areata to 1:1 in treated alopecia areata. Additional immunohistochemical investigations showed an aberrant expression of major histocompatibility complex class I, major histocompatibility complex class II and intercellular adhesion molecule 1 on keratinocytes of the mid and lower parts of hair follicles in untreated alopecia areata. In successfully treated skin ectopic major histocompatibility complex class I and II expression was clearly reduced, whereas intercellular adhesion molecule 1 expression showed only minor changes. In conclusion, alopecia areata-like hair loss in C3H/HeJ mice responded to treatment with the contact sensitizer squaric acid dibutylester analogous to human alopecia areata. Moreover, successful treatment changes the aberrant expression of major histocompatibility complex class I and II in a way similar to that observed in human alopecia areata. These observations support the concept that alopecia areata-like hair loss in C3H/HeJ mice can be utilized as an appropriate model for the study of human alopecia areata.

Allergens↗
PubMed1999

Cigarette smoking as a triggering factor of hidradenitis suppurativa.

BACKGROUND: Hidradenitis suppurativa is a chronic inflammatory skin disease involving the axillary, inguinal and anogenital regions and sometimes, in addition, the submammary or sacral areas. The etiology of this condition is unknown. OBJECTIVE: A matched-pair case-control study was performed to evaluate the influence of smoking habits on the manifestation of this disease. METHODS: Patients who had received surgical treatment for hidradenitis suppurativa in two dermatological centers completed a questionnaire dealing with family history, course of the disease and smoking habits. To form a randomized matched-pair control group, an equal number of patients admitted for various other skin diseases such as atopic dermatitis, varicose veins, skin tattoos, alopecia areata or melanoma was matched for sex and age and evaluated for smoking habits. Statistical analysis was performed by use of several chi2 tests in a cross-table setting. Moreover, a comparison to the expected smoking prevalence in Germany based on national statistics was performed. RESULTS: Out of 84 patients treated for hidradenitis suppurativa, 63 subjects (27 men, 36 women) completed the questionnaire. The rate of active cigarette smokers was 88.9% (56 patients), whereas 4 subjects (6.4%) had never smoked. 3 patients (4.8%) stated to be ex-smokers, but 2 of these had quit smoking only recently and after onset of the disease. The rate of smokers in the matched-pair control group was 46%. The significantly higher proportion of active smokers among patients with hidradenitis suppurativa can be expressed by an odds ratio of 9.4, the calculated 95% confidence interval was 3.7-23.7 (p < 0.001). The expected smoking prevalence in Germany was 26.7% according to national statistics. 73% of our patients had no family history of hidradenitis suppurativa whereas 27% reported at least one affected first-degree relative. CONCLUSION: From the exceedingly high rate of smokers among patients with this condition we conclude that cigarette smoking is a major triggering factor of hidradenitis suppurativa. Remarkably, the disease can be categorized as a smoking sequel that is neither of vascular nor neoplastic nature. Because familial occurrence was rather rarely reported, and because an environmental factor in the form of cigarette smoking appears to be of crucial importance to trigger the disease, we assume that the genetic basis of hidradenitis suppurativa is polygenic rather than mendelian. Smoking cessation should be encouraged particularly in patients with hidradenitis suppurativa although it is unknown whether this improves the course of the disease.

Adolescent↗
PubMed1999

Type 2 segmental manifestation of multiple glomus tumors: A review and reclassification of 5 case reports.

BACKGROUND: In various autosomal dominant skin disorders, segmental forms reflecting mosaicism have been reported. Recently, two different types of mosaic manifestation have been delineated. Type 1 reflects heterozygosity for the underlying mutation and shows a degree of severity as observed in the corresponding nonmosaic phenotype. Type 2 originates from loss of heterozygosity, shows an excessively severe involvement and is usually superimposed on the disseminated lesions of the ordinary trait. OBJECTIVE: We wanted to exemplify further the proposed rule of dichotomy. METHODS: We have screened the literature on multiple glomus tumors, a trait that follows an autosomal dominant mode of transmission. RESULTS: We found 5 cases of multiple glomus tumors suggesting a type 2 segmental involvement. In all of these cases, a unilateral band-like or patchy arrangement of excessively pronounced glomus tumors was associated with disseminated lesions corresponding to the ordinary phenotype, and in 3 cases other family members were affected with disseminated glomus tumors. The unilateral agminated lesions were reported to be present in early childhood, whereas the disseminated lesions appeared later. CONCLUSION: Multiple glomus tumors can be added to the list of autosomal dominant skin disorders that may show a type 2 segmental involvement.

Adolescent↗
PubMed1999

Pronounced perifollicular lymphocytic infiltrates in alopecia areata are associated with poor treatment response to diphencyprone.

Some authors have reported that severe destruction of follicular structures and even scarring patterns occur in those patients with alopecia areata (AA) who fail to respond to topical immunotherapy with contact sensitizers, such as diphencyprone (DCP). Other studies, however, gave contradictory results. Therefore, we re-examined histopathological changes in scalp samples obtained from 85 patients with severe alopecia areata before initiation of DCP treatment (40 responders and 45 non-responders in terms of hair regrowth after DCP treatment). The following parameters were evaluated: i) perifollicular lymphocytic infiltration; ii) perifollicular fibrosis, and iii) miniaturized hair follicles. No difference between responders and non-responders could be observed in the degree of miniaturization of hair follicles and proliferation of perifollicular fibrous tissue. In neither group was there any evidence of scarring or severe follicular destruction. 18 non-responders but only 6 responders showed a very dense perifollicular lymphocytic infiltration. In contrast, a particularly scarce infiltrate was seen in 9 non-responders and in 19 responders. We conclude that non-responders to topical sensitizers tend to have rather pronounced inflammatory reactions with dense perifollicular lymphocytic infiltrates.

Administration, Topical↗
PubMed1999

Type 2 segmental Darier disease.

A 45-year-old man had bilateral disseminated involvement of Darier disease, and two of his sisters likewise had lesions suggesting this trait. Remarkably the propositus showed, in addition, a unilateral, systematized, segmental pattern of excessively pronounced Darier lesions. This unusual case can be taken as an example of type 2 segmental Darier disease. In contrast to the type 1 segmental manifestation that develops from a new mutation occurring in an otherwise healthy embryo, the type 2 segmental involvement would originate in a heterozygous embryo from postzygotic loss of the corresponding normal allele, resulting in a cell clone that is either homozygous or hemizygous for the mutation. This concept would explain why the segmental lesions were excessively pronounced and superimposed on the ordinary trait. Future studies may show whether the concept of type 2 segmental Darier disease can be confirmed at the molecular level.

Biopsy, Needle↗
PubMed1999

Linear porokeratosis superimposed on disseminated superficial actinic porokeratosis: report of two cases exemplifying the concept of type 2 segmental manifestation of autosomal dominant skin disorders.

A concept of dichotomous types of segmental involvement of autosomal dominant skin disorders has recently been proposed. Among the different types of porokeratosis, disseminated superficial actinic porokeratosis is known to be an autosomal dominant skin disorder, and linear porokeratosis represents the segmental form of the disease. We intended to exemplify the type 2 segmental manifestation within this concept. Clinical and histopathologic aspects of porokeratotic lesions of 2 patients were investigated. The family history was studied in both cases. Linear porokeratosis superimposed on disseminated superficial actinic porokeratosis was observed in both patients. These 2 cases of linear porokeratosis associated with disseminated superficial actinic porokeratosis can be taken as further examples of a type 2 segmental involvement occurring in an autosomal dominant skin disorder.

Female↗
PubMed1998

Dyskeratosis congenita with linear areas of severe cutaneous involvement.

Dyskeratosis congenita (DC) is a rare hereditary disorder of skin which may be associated with aplastic anemia. The pattern of inheritance is X-linked recessive in most instances, but autosomal dominant and autosomal recessive types have been documented. Reticulated hyperpigmentation usually is the first manifestation. The pigmentary changes may be limited to neck, upper chest, and proximal parts of the limbs initially but within affected areas the involvement is always diffuse. We report on a patient with typical diffuse cutaneous signs of dyskeratosis congenita superimposed with hyperpigmentation that was more pronounced along Blaschko's lines. To explain this phenomenon, we assume that the patient has the autosomal dominant type and that loss of heterozygosity occurred in a somatic cell giving rise to a population of cells that migrated along these lines during embryogenesis.

Adolescent↗
PubMed1998

Congenital ichthyosis, follicular atrophoderma, hypotrichosis, and hypohidrosis: a new genodermatosis?

Follicular atrophoderma is a rare anomaly observed mainly in the X-dominant form of chondrodysplasia punctata (Conradi-Hünermann-Happle syndrome) and in the X-linked dominant Bazex syndrome. We report on five Emirati sibs (three girls and two boys), 4-18 years old, with normal stature, diffuse congenital ichthyosis, patchy follicular atrophoderma, generalized and diffuse non-scarring hypotrichosis, and marked hypohidrosis. Steroid sulfatase activity, assessed in the two boys, was found to be normal. Electron microscopic studies of ichthyotic skin did not show any specific abnormality. The association of congenital diffuse ichthyosis with follicular atrophoderma and hypotrichosis has not been reported before. The patients were reminiscent of Bazex syndrome; however, ichthyosis is not a component of Bazex syndrome. We conclude that this syndrome of congenital ichthyosis with follicular atrophoderma represents a new autosomal recessive genodermatosis.

Abnormalities, Multiple↗