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P Freyschmidt-Paul

Publications and source records attributed to P Freyschmidt-Paul.

At least 19 recordsLinked to original sources
PubMed2006

Alterations in the epidermal-dermal melanin axis and factor XIIIa melanophages in senile lentigo and ageing skin.

BACKGROUND: Senile lentigo (SL) is a pigmentation disorder that occurs predominantly on the dorsa of the hands, the forearms and the face; its incidence increases with age. Histological hallmarks of SL lesions are hyperpigmentation of the epidermis and elongation of the epidermal rete ridges. Various factors such as alpha-melanocyte-stimulating hormone, endothelin-1 or stem cell factor are involved in the onset and maintenance of the increased pigmentation. Alterations of the dermal compartment have not yet been analysed in detail in SL. OBJECTIVES: To study the occurrence and distribution of melanin in the dermis from SL and aged skin, biopsies from 12 subjects were morphologically analysed by light and electron microscopy in comparison with unaffected skin. METHODS: Punch biopsies of SL and adjacent skin from 12 male or female volunteers aged 52-81 years were prepared for light and electron microscopy and samples were analysed by morphological, morphometric, histochemical and immunohistochemical methods. RESULTS: The epidermis from SL revealed morphological features such as hyperpigmentation of basal keratinocytes and the formation of elongated rete ridges. S100+ melanocytes in the stratum basale were not markedly increased, indicating that the hyperpigmentation is predominantly due to changes in melanin synthesis, distribution or turnover. Quantification of epidermal cells expressing the proliferation marker Ki67 did not show an increase of this parameter in SL, indicating that at least in the established lesion cell proliferation is not enhanced. We further focused on the dermal compartment and observed granulated cells which were more abundant in SL. Electron microscopic and histochemical analysis revealed that the granulation of these cells is based on melanosomes, mostly present in large melanosomal complexes. Immunohistochemistry using antibodies to CD68 and factor XIIIa (FXIIIa) showed these melanophages to be predominantly FXIIIa+ dermal dendrocytes, which were about six times more abundant than CD68+ macrophages. CONCLUSIONS: In SL an increased number of melanophages was found compared with unaffected skin from the same subject. These melanophages were identified as FXIIIa+ dermal dendrocytes. Possible functional consequences of the massive melanin uptake by dermal dendrocytes are discussed.

Aged↗
PubMed2006

Interferon-gamma-deficient mice are resistant to the development of alopecia areata.

BACKGROUND: Alopecia areata (AA) is a T-cell mediated putative autoimmune disease of hair follicles, which can be transferred by CD4(+) T cells. However, whether T-helper (Th) 1 or Th2 cytokines are predominant has not yet been defined. OBJECTIVES: To elucidate the importance of Th1 cells in the pathogenesis of AA we investigated the functional role of interferon (IFN)-gamma in the experimental induction of AA. METHODS: AA was experimentally induced by grafting full-thickness skin from AA-affected C3H/HeJ mice on to C3H/HeJ mice with a targeted deletion of the Th1 cytokine IFN-gamma gene (IFNgamma(-/-)) and on to wild-type mice (IFNgamma(+/+)). RESULTS: While 90% of wild-type mice developed AA, none of the IFNgamma(-/-) mice exhibited hair loss. Immunohistochemistry of skin sections revealed a dense perifollicular and intrafollicular infiltrate of CD4(+) and CD8(+) T cells in controls, while in IFNgamma(-/-) mice skin-infiltrating CD8(+) T cells were absent and the number of CD4(+) cells was significantly reduced. Aberrant expression of major histocompatibility complex class I and II molecules in the putative immune-privileged infrainfundibular site of the hair follicle was found to be weaker in AA-resistant IFNgamma(-/-) mice than in control mice with AA. Flow cytometry revealed that leucocytes of IFNgamma(-/-) mice did not respond to the transfer of AA-affected skin. As distinct from IFNgamma(+/+) mice, neither T-cell activation markers nor Th1 cytokines were upregulated in draining lymph node cells or skin-infiltrating leucocytes of AA-resistant IFNgamma(-/-) mice. However, there was no evidence for a shift towards a Th2 cytokine profile, nor for upregulation of regulatory T cells in IFNgamma(-/-) mice. CONCLUSIONS: IFNgamma(-/-) mice fail to activate Th1 cells in response to the transplanted (auto)antigens, which suggests an essential requirement for IFN-gamma-mediated Th1 activation in the induction of AA.

Alopecia Areata↗
PubMed2004

Chronic delayed-type hypersensitivity reaction as a means to treat alopecia areata.

The acute phase of alopecia areata (AA) is characterized by an increase in CD44v3+ and CD44v10+ skin-infiltrating leucocytes (SkIL). Induction of a contact eczema, one of the therapeutic options in AA, can be mitigated strongly by a blockade of CD44v10. The observation that induction of a delayed type hypersensitivity (DTH) reaction abrogates an autoimmune reaction, where both responses apparently use similar effector mechanisms, is surprising and prompted us to search for the underlying mechanisms. AA-affected C3H/HeJ mice were treated with the contact sensitizer SADBE (squaric acid dibutylester) and leucocyte subpopulations and their activation state was evaluated in SkIL and draining lymph nodes. AA-affected mice exhibited an increased number of SkIL with a predominance of T lymphocytes. After treatment with the contact sensitizer SADBE recovery of SkIL was reduced and monocytes predominated. However, a significantly increased number of leucocytes was recovered from draining lymph nodes. Draining lymph node cells from untreated and treated AA mice exhibited all signs of recent activation with high-level expression of co-stimulatory and accessory molecules and an increased percentage of CD44v3+ and CD44v10+ leucocytes. In contrast, SkIL of SADBE-treated AA mice contained relatively few activated T cells and reduced numbers of CD44v3+ and CD44v10+ cells. Thus, the activation state and the distribution of leucocyte subsets in SADBE-treated AA mice are consistent with a blockade of leucocyte extravasation. Accordingly, the therapeutic effect of long-term SADBE treatment may rely on impaired leucocyte traffic.

Allergens↗
PubMed2003

[Alopecia areata. Clinical aspects, pathogenesis and rational therapy of a T-cell-induced autoimmune disease].

Alopecia areata is a T-cell mediated autoimmune disease directed against an unknown auto antigen of the hair follicle. There is a genetic predisposition to develop alopecia areata, whereas environmental triggers have so far not been identified. The diagnosis can be established by characteristic clinical features of alopecia areata including its severe forms alopecia areata totalis and universalis. Nail changes may help confirm the diagnosis. On rare occasions a histopathological examination may be necessary, whereas other laboratory investigations are unnecessary. Because of the high rate of spontaneous remission, the efficacy of a rational treatment of alopecia areata has to be proven in controlled studies and it should be associated with only minor side effects. According to the rules of evidence-based medicine, treatment with a contact sensitizer is at present the most effective treatment of alopecia areata showing only mild side effects. However, it is time-consuming and in some cases ineffective, making it desirable to develop new, more specific forms of treatment.

Alopecia Areata↗
PubMed2003

Dietary soy oil content and soy-derived phytoestrogen genistein increase resistance to alopecia areata onset in C3H/HeJ mice.

Alopecia areata (AA) is a complex, multi-factorial disease where genes and the environment may affect susceptibility and severity. Diet is an environmental factor with the potential to influence disease susceptibility. We considered dietary soy (soya) oil content and the soy-derived phytoestrogen genistein as potential modifying agents for C3H/HeJ mouse AA. Normal haired C3H/HeJ mice were grafted with skin from spontaneous AA affected mice, a method previously shown to induce AA. Grafted mice were given one of three diets containing 1%, 5% or 20% soy oil and observed for AA development. In a separate study, mice on a 1% soy oil diet were injected with 1 mg of genistein three times per week for 10 weeks or received the vehicle as a control. Of mice on 1%, 5%, and 20% soy oil diets, 43 of 50 mice (86%), 11 of 28 mice (39%), and 2 of 11 mice (18%) developed AA, respectively. Four of 10 mice injected with genistein and 9 of 10 controls developed AA. Mice with AA had hair follicle inflammation consistent with observations for spontaneous mouse AA, but no significant association was observed between the extent of hair loss and diet or genistein injection. Mice that failed to develop AA typically experience white hair regrowth from their skin grafts associated with a moderate macrophage and dendritic cell infiltration. Soy oil and derivatives have previously been reported to modify inflammatory conditions. Hypothetically, soy oil compounds may act on C3H/HeJ mice through modulating estrogen-dependent mechanisms and/or inflammatory activity to modify AA susceptibility.

Alopecia Areata↗
PubMed2001

SKIBO diseases: a concept to avoid bloody diagnostic procedures in ambiguous skeletal lesions.

In cases with an "atypical" radiologic pattern-osteolytic as well as osteosclerotic or mixed - the radiologist should pay attention to the patient's skin. There he will often find specific changes that are the key to a correct interpretation of the radiologic abnormalities. In such cases the synopsis is of more value in differential diagnosis than more or less unspecific histologic findings. Entities with a non-arbitrary conjunction of changes of the skin and bones we call SKIBO diseases. Some of them have a high potential for mimicking malignant bone lesions, often with the consequence of unnecessary biopsies. In this article we present the typical dermatologic and radiologic signs and symptoms of neurofibromatosis, sarcoidosis and pustulotic arteroosteitis (PAO) with special focus on such skeletal lesions that may mimic malignancy.

Bone Neoplasms↗
PubMed2001

Pitfalls of irritant patch testing using different test chamber sizes.

BACKGROUND: Test chambers for irritant patch testing are usually larger than those used in allergic patch testing. In general, larger areas show stronger skin reactions than smaller areas. OBJECTIVE: This study investigated whether this difference is of practical relevance, when a model irritant is applied in small and large Finn chambers and evaluated by measurement of transepidermal water loss (TEWL). METHODS: Patch testing was performed with 2 concentrations of sodium lauryl sulfate (SLS) (0.25% and 0.5%) on forearms of healthy volunteers. Large (inner diameter, 12 mm) and small (inner diameter, 8 mm) chambers were used. RESULTS: A variance analysis (3 factors, 2-tailed) showed that the test outcome, as assessed by TEWL, was strongly dependent on SLS test concentration and test chamber size. The larger chambers gave approximately 30% to 50% higher values than the smaller. CONCLUSIONS: This may be explained by the fact that with the small chambers, the adjacent small area of nontreated skin was also assessed by the evaporimeter, biasing the results. A formula estimating TEWL value of the large chamber from values of the small chambers has been proposed.

Adolescent↗
PubMed2001

Current and potential agents for the treatment of alopecia areata.

Alopecia areata is considered to be a T-cell mediated autoimmune disease of the hair follicle. Current immunosuppressive approaches and immunomodulatory treatment with contact sensitizers such as diphenylcyclopropenone and squaric acid dibutylester are dealt with in this review article. The efficacy of the various modes of treatment is evaluated by a review of literature and their mode of action is discussed. In accordance with the mechanism of autoimmune pathogenesis of AA, improved future treatments may be immunosuppressive or immunomodulatory, or they should otherwise protect the hair follicle from the injurious effects of the inflammation. Such possible future therapeutic approaches include the use of liposomes as an improved vehicle, application of immunosuppressive cytokines like TGF-beta and IL-10, inhibition of apoptosis mediated by the Fas-FasL system, inhibition of the lymphocyte homing receptor CD44v10, induction of tolerance as well as principles of gene therapy.

Adjuvants, Immunologic↗
PubMed2000

Treatment with an anti-CD44v10-specific antibody inhibits the onset of alopecia areata in C3H/HeJ mice.

A murine CD44v10-neutralizing antibody has been reported to impair delayed-type hypersensitivity reactions. Because alopecia areata is characterized by a delayed-type hypersensitivity-like T cell mediated immune response, we addressed the question whether an anti-CD44v10-antibody influences the onset of alopecia areata. Therefore, we used the C3H/HeJ mouse model with the induction of alopecia areata in unaffected mice by the grafting of lesional alopecia areata mouse skin. Six grafted mice were injected (intraperitoneally) with anti-CD44v10, six grafted mice with anti-CD44standard, and six with phosphate-buffered saline only. After 11 wk phosphate-buffered saline injected animals on average had developed alopecia areata on 36.8% of their body. The onset of hair loss was slightly delayed and its extent reduced to 17.2% of their body in anti-CD44standard-treated mice. By contrast, five of six anti-CD44v10-treated mice did not show any hair loss and one mouse developed alopecia areata on only 1% of the body. Immunohistochemical examination revealed a marked reduction of perifollicular CD8+ lymphocytes and, to a lesser degree, CD4+ cells as well as a decreased expression of major histocompatibility complex class I on hair follicle epithelium in anti-CD44v10-treated mice as compared with phosphate-buffered saline or anti-CD44 standard-treated mice. Our data show that anti-CD44v10 is able to inhibit the onset of alopecia areata in C3H/HeJ mice. This might be accomplished by an anti-CD44v10-triggered impairment of immune cell homing (e.g., CD8+ T cells), resulting in a decrease of their number in target tissues.

Alopecia Areata↗
PubMed2000

Normalisation of hair follicle morphology in C3H/HeJ alopecia areata mice after treatment with squaric acid dibutylester.

Alopecia areata is a non-scarring, reversible disorder, presumably caused by an autoimmune attack on anagen hair follicles. Treatments are numerous, and most of these are ineffective. However, the elicitation of contact dermatitis on the affected skin is commonly associated with hair regrowth. A major advance in the study of alopecia areata has been the introduction and characterisation of the C3H/HeJ mouse model that exhibits many features of the human disease. In this study we examined the effects of squaric acid dibutylester treatment on hair follicles and the associated leukocyte infiltrate in alopecia areata mice by light and transmission electron microscopic analysis. This was compared with unaffected normal mice and alopecic untreated mice. Experimental mice were treated unilaterally with the contact allergen squaric acid dibutylester and the skin was assessed after hair regrowth. The characteristic pathological picture of alopecia areata was observed in alopecic but not normal mice. Nine of eleven experimental mice regrew hair on the treated side only and this was associated with a reduction in peri/intrafollicular inflammatory cell infiltrates, hair follicle dystrophy, melanin incontinence/clumping, and an increase in the numbers of hair follicles in full anagen. This normalisation of hair follicle status after treatment reflects the successful reversal of disease in these mice. The mechanism of action of topical immunotherapy with a potent contact allergen such as squaric acid dibutylester still needs to be elucidated, but an altered immune milieu is suspected. This study further validates the C3H/HeJ mouse model of alopecia areata in the search for therapeutic interventions in this common hair follicle disorder.

Adjuvants, Immunologic↗
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

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

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

[Neonatal lupus erythematosus and maternal HELLP syndrome: is there a pathogenetic link?].

A newborn boy developed annular erythematous lesions on his entire body. Histopathological examination showed typical features of lupus erythematosus. His mother was positive for anti-Ro/SSa and anti-La/SSb antibodies. Neonatal lupus erythematosus was diagnosed. During pregnancy the mother had suffered from HELLP syndrome. The reported case points out the necessity to differentiate HELLP syndrome from first manifestation of lupus erythematosus during pregnancy. A direct causal relationship between neonatal lupus erythematosus and HELLP syndrome of the mother seems to be unlikely.

Adult↗
PubMedDate not supplied

Genetic susceptibility and severity of alopecia areata in human and animal models.

Alopecia areata (AA) is a non-scarring, inflammatory form of hair loss. Human and animal model observations suggest that AA is an autoimmune mediated disease. Genetic influence has been clearly demonstrated in many other autoimmune diseases and one would expect that AA is no exception. AA in rodent models involves genetic susceptibility and it is possible to cross breed the AA phenotype to unrelated rodent strains. Segregation analysis of rodent breeding programs suggests the involvement of several dominant and secondary genes. The increased frequency of AA in genetically related individuals, suggests that human AA expression also involves genetic susceptibility. Within the general population, AA does not segregate as a Mendelian, monogenic trait. AA is a continuous trait with varying degrees of hair loss within the affected population. This suggests that human AA expression involves a complex interaction of multiple genes. AA is most likely a polygenic disease where several, potentially identifiable, major genes affect disease susceptibility and minor severity modifying genes may further affect the phenotype. Here we review the literature on humans and animal models for AA to identify data in support of AA as a polygenic, multivariate penetrance disease with a threshold level for disease onset. Genome wide allelic association screening of animal models and genetically related human sibling pairs may be a suitable approach to identifying susceptibility and severity modifying genes for AA.

Alopecia Areata↗
PubMedDate not supplied

Trichoteiromania.

We describe a 61-year-old patient who compulsively rubbed her hair and her scalp because of a psychiatric disorder. Permanent rubbing resulted in fracturing of the hair shafts, leaving 2 cm long hairs and areas with stubs of 1mm length, giving the impression of bald spots. The distal ends of affected hair shafts were split, giving the impression of white tips. Light microscopy of the hair shafts showed split, brush-like ends of otherwise normal hair. We suggest the name trichoteiromania, which means "compulsive rubbing of hair", as a new term to describe hair loss in such cases.

Alopecia↗