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Biomedical subjects

D Metze

Publications and source records attributed to D Metze.

At least 19 recordsLinked to original sources
PubMed2001

Overexpression of CD40 ligand in murine epidermis results in chronic skin inflammation and systemic autoimmunity.

CD40-CD40 ligand (L) interactions play a pivotal role in immune-mediated inflammatory responses via the activation of antigen-presenting cells (APCs). To investigate the effects of continuous activation of resident tissue APCs, in this case the Langerhans cells (LCs) of the skin, CD40L expression was targeted to the basal keratinocytes of the epidermis of mice using the keratin-14 promoter. Approximately 80% of the transgenic (Tg) mice spontaneously developed dermatitis on the ears, face, tail, and/or paws. Compared with littermates, Tgs had a >90% decrease in epidermal LCs yet increased numbers within the dermis suggestive of enhanced emigration of CD40-activated LCs. Tgs also displayed massive regional lymphadenopathy with increased numbers of dendritic cells and B cells. Moreover, a decrease in IgM and an increase in IgG1/IgG2a/IgG2b/IgE serum concentrations was detectable. Screening for autoantibodies revealed the presence of antinuclear antibodies and anti-dsDNA antibodies implicative of systemic autoimmunity. Accordingly, renal Ig deposits, proteinuria, and lung fibrosis were observed. Adoptive transfer of T cells from Tgs to nonTg recipients evoked the development of skin lesions similar to those found in the Tgs. Dermatitis also developed in B cell-deficient CD40L Tg mice. These findings suggest that in situ activation of LCs by CD40L in the skin not only leads to chronic inflammatory dermatitis but also to systemic mixed-connective-tissue-like autoimmune disorders, possibly by breaking immune tolerance against the skin.

Animals↗
PubMed2001

Intracellular persistence of Staphylococcus aureus small-colony variants within keratinocytes: a cause for antibiotic treatment failure in a patient with darier's disease.

Intracellular persistence assays were performed with small-colony variants (SCVs) derived from a patient with Darier's disease from whom different phenotypes and genotypes of Staphylococcus aureus were isolated over a 28-month period; the assays revealed that >100-fold more SCV cells persisted intracellularly relative to the normal phenotype. The presence of intracellular S. aureus SCVs may protect against host defenses and antibiotic therapy and thus may have contributed to this patient's very prolonged skin infection.

DNA, Bacterial↗
PubMed2001

[Familial dyskeratotic comedones. A rare entity].

Familial dyskeratotic comedones is a rare autosomal dominant genodermatosis. In childhood or adolescence disseminated keratotic papules develop and gradually increase in number with time. The isolated papules show a central keratotic plug which tends to recur after extraction. Pruritus and occasional inflammation are the only symptoms. The lesions appear on the extremities, and less frequently on the trunk and the face. About half of the patients have a history of acne vulgaris. The histologic picture is highly characteristic and shows a deep invagination of an acantholytic and dyskeratotic epidermis with prominent cornification. Familial dyskeratotic comedones are generally refractory to any therapy. We report on two sisters with familial dyskeratotic comedones successfully treated by CO2-laser therapy.

Adult↗
PubMed2001

[Imiquimod: a new treatment possibility in bowenoid papulosis?].

Bowenoid papulosis is a highly characteristic condition of the anogenital region which is histologically similar to bowenoid carcinoma in situ. Some evidence suggests a viral origin on the basis of infection with high-risk oncogenic genotypes of human papilloma viruses (HPV 16/18 and others) and an association with cervical carcinoma. Malignant transformation is rare in bowenoid papulosis. The condition usually shows a good response to immuno-modulatory treatment. In the following we present our first case of successful treatment with imiquimod, a topical immune response modifier which is successfully used in the USA for local treatment of condylomata acuminata. Imiquimod creme (Aldara) proved to be a safe, efficious and practical patient-applied therapeutic option for the treatment of bowenoid papulosis. In view of the oncogenic potential of high-risk HPV infections, irrespective of the treatment used, all patients with bowenoid papulosis and their sexual partners must be included in long-term follow-up and regularly examined for malignant transformation.

Adjuvants, Immunologic↗
PubMed2001

[Large melanocytic nevi in generalized atrophic benign epidermolysis bullosa (epidermolysis bullosa nevi)].

Generalized atrophic benign epidermolysis bullosa (GABEB) is a nonlethal form of junctional epidermolysis bullosa. The expression of type XVII collagen (180 kDa bullous pemphigoid antigen) or of laminin 5 is markedly reduced in the skin. A 13-year-old patient with GABEB, developed several large, asymmetric, irregularly pigmented melanocytic nevi with poorly defined borders. They had appeared following blister formation since 8 years of age. Histological examination revealed an irregular proliferation of monomorphous melanocytes at the dermoepidermal junction. Small nests of melanocytes were focally present. This case further emphasizes the difficulty in differentiating nevi appearing in GABEB from malignant melanoma.

Adolescent↗
PubMed2001

[Endometrial metastasis of a "balloon" cell melanoma mimicking a "xanthomatous endometritis"].

Xanthomatous changes are unusual lesions of the corpus endometrium that may mask endometrial carcinoma. The term "xanthomatous endometritis" refers to morphological changes frequently induced by estrogen stimulation. We report for the first time a case of uterine metastasis of balloon-cell melanoma mimicking xanthomatous endometritis. Light microscopic, immunohistological, and ultrastructural results are presented and discussed in connection with our ideas on the pathogenesis of this peculiar tumor. The findings favor the hypothesis of a regressive phenomenon in the balloon-cell transformation of melanoma cells. The melan-A immunohistology seems to be more important in the diagnosis of balloon cell melanoma than the classic melanoma antibody HMB 45.

Diagnosis, Differential↗
PubMed2001

Differential storage of hydroxyethyl starch (HES) in the skin: an immunoelectron-microscopical long-term study.

Hydroxyethyl starch (HES) is widely used as a plasma substitute. Serious side effects occur only rarely, whereas a high incidence of severe pruritus has been reported. Moreover, tissue storage of HES has been demonstrated in various organs. The aim of the current study has been to examine precisely the intracellular uptake and long-term storage of HES in the skin. Skin biopsies from 119 patients who received HES of various preparations and cumulative dosage were obtained 30 min to 130 months after infusion therapy. The samples were analysed by ultrastructural and immunoelectron microscopy with HES-specific monoclonal and polyclonal antibodies. A characteristic vacuolisation of perivascular histiocytes was a regular finding in all skin biopsies as early as 1 day after a single infusion of 30 g. Immunoreactivity for HES was demonstrable within the vacuoles. Generally, the size and number of vacuoles in the histiocytes increased concomitantly with the cumulative dosage. Following administration of higher HES dosages, vacuoles were demonstrable in endothelial cells of blood and lymphatic vessels, basal keratinocytes, epithelia of sweat glands and in small peripheral nerves, the last mentioned being associated with pruritus. A subsequent reduction of the vacuoles in size and number could be demonstrated within 52 months. In nerves, HES deposits persisted no longer than 17 months paralleling the cessation of pruritus. Biopsies taken after 94 months exhibited no HES deposits in the skin. The condensation and final dissolution of the vacuoles may either indicate the release and subsequent redistribution of HES into the circulation or lysosomal degradation.

Adolescent↗
PubMed2001

Human dermal fibroblasts express prohormone convertases 1 and 2 and produce proopiomelanocortin-derived peptides.

In the last few years it has become apparent that the skin is a locoregional source for several proopiomelanocortin-derived peptides including alpha-melanocyte-stimulating hormone, adrenocorticotropin, and beta-endorphin. The enzymes that regulate expression of these neuropeptides are the prohormone convertases 1 and 2. In this study we demonstrate, by reverse transcriptase polymerase chain reaction and Western immunoblotting, that cultured human dermal fibroblasts express prohormone convertases 1 and 2 as well as 7B2, which is an essential cofactor for enzymatic activity of prohormone convertase 2. Immunofluorescence studies revealed prohormone convertase 1 to be mainly expressed in the perinuclear region in vesicular structures resembling the trans-Golgi network, whereas prohormone convertase 2 was found in the trans-Golgi network as well as in vesicular structures diffusely distributed in the peripheral cytoplasm. Expression of both enzymes was also confirmed in fibroblasts of normal adult human skin by immunohistochemistry using antibodies against prohormone convertases 1 and 2 and vimentin. To assess the relevance of prohormone convertase 1 and 2 expression in human dermal fibroblasts, we studied the expression of proopiomelanocortin and proopiomelanocortin-derived peptides. Proopiomelanocortin expression was detected by reverse transcriptase polymerase chain reaction and Western immunoblotting. Alpha-melanocyte-stimulating hormone, adrenocorticotropin, and beta-endorphin were mainly located in vesicular structures as demonstrated by immunofluorescence. Production of these peptides was confirmed by radioimmunoassay, immunoradiometric assay, or enzyme immunoassay. Among several stimuli tested, interleukin-1 was found to upregulate production of alpha-melanocyte-stimulating hormone in human dermal fibroblasts. In summary, we have shown that human dermal fibroblasts express the enzymatic machinery for proopiomelanocortin processing and make proopiomelanocortin, alpha-melanocyte-stimulating hormone, adrenocorticotropin, and beta-endorphin. Production of proopiomelanocortin peptides by human dermal fibroblasts may be relevant for fibroblast functions such as collagen degradation and/or regulation of dermal immune responses.

Adrenocorticotropic Hormone↗
PubMed2001

A localized variant of paraneoplastic pemphigus: acantholysis associated with malignant melanoma.

We report a 72-year-old male patient with a nodular malignant melanoma that was associated with focal suprabasal acantholysis (FSA). This phenomenon, which is regarded as an incidental finding by dermatopathologists, may be associated with inflammatory and also neoplastic skin diseases. Haematoxylin and eosin stained sections from an erythematous plaque surrounding the patient's tumour showed FSA, direct immunofluorescence (DIF) and indirect immunofluorescence (IIF) on normal human skin, monkey oesophagus and rat urinary bladder were negative. On electron microscopy few desmosomes could be detected in the basal cell layer of the acantholytic areas and there was a nearly complete loss of these structures in the spinous cell layer. Only remnants of cytoplasmic plaques and keratin filaments could be observed in those areas. In contrast, adherens junctions appeared to be well preserved. An enzyme-linked immunosorbent assay (ELISA) using recombinant fusion proteins as antigens did not show circulating autoantibodies against desmoglein 1 (Dsg1) or desmoglein 3 (Dsg3). In contrast, immunoblotting revealed autoantibodies directed against keratinocyte antigens with a molecular weight of 85 kDa and 250 kDa, the first band corresponding to the molecular weight of comigrating plakoglobin. Immunoprecipitation with patient serum also revealed a 85-kDa band. We conclude that these autoantibodies, probably in conjunction with cofactors produced by the tumour, could play a part in the pathogenesis of this variant of FSA, for which we propose the term 'localized paraneoplastic pemphigus.'

Acantholysis↗
PubMed2001

Treatment of prurigo nodularis with topical capsaicin.

BACKGROUND: Prurigo nodularis is an eruption of lichenified or excoriated nodules caused by intractable pruritus that is difficult to treat. Therefore the antipruritic efficacy of capsaicin seemed to be of particular interest because this alkaloid, extractable from red pepper, interferes with the perception of pruritus and pain by depletion of neuropeptides in small sensory cutaneous nerves. OBJECTIVE: The aim of this concentration- and regimen-ranging study was to evaluate the efficacy, safety, and practicability of capsaicin in the topical treatment of prurigo nodularis in a large series of patients. METHODS: A total of 33 patients with prurigo nodularis of various origins were selected to receive capsaicin (0.025% to 0.3%) 4 to 6 times daily for 2 weeks up to 10 months. The consecutive follow-up period was up to 6 months. In 7 patients, skin biopsy specimens were taken before, during, and after therapy and investigated histologically, immunohistochemically, and ultrastructurally. RESULTS: All 33 patients could be evaluated for efficacy. After cessation of the symptoms of neurogenic inflammation, such as burning sensations or erythema, all of them experienced a complete elimination of pruritus within 12 days. In addition, capsaicin largely contributed to the gradual healing of the skin lesions. After discontinuation of the therapy, pruritus returned in 16 of 33 patients within 2 months. At the ultrastructural level, no degenerative changes of cutaneous nerves could be found during or after capsaicin therapy. Depletion of substance P was demonstrated by confocal laser scanning microscopy thus confirming the specific effect of capsaicin in vivo. CONCLUSION: Topical treatment of prurigo nodularis with capsaicin proved to be an effective and safe regimen resulting in clearing of the skin lesions.

Administration, Topical↗
PubMed2001

Diffuse melanosis arising from metastatic melanoma: pathogenetic function of elevated melanocyte peptide growth factors.

The origin of diffuse melanosis resulting from metastatic melanoma is unknown. We examined the light microscopic and ultrastructural changes in the skin of an affected 35-year-old woman and determined the peripheral blood levels of melanocyte growth factors. A total of 7 biopsy specimens were examined by light and electron microscopy and immunohistology (S-100, HMB45, MART1, CD68, MAC387). Serum/plasma levels of melanocyte growth factors of the patient were determined by enzyme-linked immunosorbent assays and compared with those of normal volunteers (n = 10) and amelanotic patients with metastatic melanoma (n = 10), matched to the UICC stage of the affected patient. Hyperpigmented but otherwise apparently normal skin of the patient displayed epidermal melanocyte hyperplasia, increased melanogenesis, and dermal pigment stored in histiocytes and other cells along with extracellular deposits. Blood levels of alpha-melanocyte stimulating hormone, hepatocyte growth factor, and endothelin-1 were significantly elevated in the affected patient. Aberrant production of these factors may not only be responsible for activation of the pigment system in diffuse melanosis of metastatic melanoma, but also for increased proliferation, motility, and pigment incontinence of normal and malignant melanocytes.

Adult↗
PubMed2000

Primary cutaneous follicle center cell lymphoma with follicular growth pattern.

Cutaneous B-cell infiltrates showing a prominent follicular growth pattern with germinal centers are thought by some authors to represent either marginal zone lymphomas with reactive germinal centers or pseudolymphomas. To establish whether a true primary cutaneous follicular lymphoma exists, we studied biopsies from 15 patients with skin lesions characterized histopathologically by the presence of B-cell infiltrates with follicular pattern. Staging investigations, including bone marrow biopsy, were negative in all patients. All were negative for bcl-2 protein expression and did not present the t(14;18). In all biopsy specimens neoplastic follicles showed 1 or more morphologic or immunophenotypic criteria of malignancy (presence of a reduced mantle zone, absence of tingible body macrophages, reduced proliferation rate). In 9 specimens a monoclonal rearrangement of J(H) genes could be detected by polymerase chain reaction analysis. After laser beam microdissection, a band of the same length could be observed in 6 probes from different follicles from the same specimen, indicating the presence of the same monoclonal population of follicle center cells. Follow-up examinations in all patients revealed no evidence of extracutaneous spread (mean follow-up, 48.7 months). Our study demonstrates that primary cutaneous follicular lymphoma represents a distinct entity of the cutaneous B-cell lymphomas. (Blood. 2000;95:3922-3928)

Adult↗
PubMed2000

[Hydroxyethyl starch accumulation in the skin with special reference to hydroxyethyl starch-associated pruritus].

BACKGROUND AND OBJECTIVE: Hydroxyethyl starch (HES) is a colloidal infusion fluid that has for a long time been used in emergency situations and to improve impaired blood perfusion. In the last few years there have been numerous reports about treatment resistant pruritus, often persisting for months, after HES infusion. We investigated the intracellular uptake of HES in the skin, special attention being focused on associated pruritus. PATIENTS AND METHODS: Skin biopsies were obtained from 120 patients (120 men, 35 women) and examined immunohistochemically and for their ultrastructure. Three patients had received various HES preparations, while 22 had been given dextran. Five patients who had received no infusions served as controls. RESULTS: All patients given HES had lysosomal deposits in the histiocytes, some of them also in cutaneous epithelium and endothelium. The extent of lysosomal storage correlated with the amount of infused HES and the interval between biopsy and last HES infusion. Consecutive biopsies in some cases demonstrated a definite decrease over the years of HES deposits in the vacuoles. This suggests that HES is regularly metabolized in the skin. Pruritus after high cumulative doses of HES was closely correlated with HES deposition in cutaneous nerves. CONCLUSIONS: These results emphasize the need for starch derivatives that can be better metabolized and for better adapted infusion schedules to reduce the high incidence of pruritus.

Adolescent↗
PubMed2000

[Hyperkeratosis lenticularis perstans (Flegel's disease) - a complex disorder of epidermal differentiation with good response to a synthetic vitamin D3 derivate].

Hyperkeratosis lenticularis perstans (Flegel's disease) is a rare but clinically and histologically highly characteristic genodermatosis. We report on new immunohistochemical and ultrastructural findings suggesting a complex disorder of epidermal differentiation. In this context, a good response to calcipotriol, a synthetic vitamin D3 derivative is of particular interest.

Aged↗
PubMed2000

[Topical administration of capsaicin in dermatology for treatment of itching and pain].

BACKGROUND AND OBJECTIVES: Treatment of pruritus as observed in many dermatological and internal diseases may be very often disappointing. There are many reports describing the topical use of capsaicin, the pungent agent in red pepper. Long term administration of capsaicin depletes neuropeptides in unmyelinated, polymodal C-type and small myelinated A delta-type cutaneous nerves that conduct pruritus and pain. PATIENTS/METHODS: The aim of this study was to evaluate the efficacy, safety and practicability of capsaicin in the treatment of pruritus and pain of different origin in a total of 40 patients. RESULTS: Capsaicin suppressed completely itch in all patients. CONCLUSIONS: In addition to its excellent antipruritic and analgetic effect, capsaicin significantly contributed to healing of some dermatoses, such as prurigo nodularis and psoriasis.

Administration, Topical↗
PubMed2000

[Specific skin infiltration of extracutaneous B-cell lymphoma in healing herpes simplex skin].

Both herpes simplex and herpes zoster are not uncommon in patients affected by malignant lymphoma or leukemia. Of particular interest, the herpetic lesions may be followed by specific cutaneous infiltrates. We report on a patient with a centrocytic-centroblastic non-Hodgkin lymphoma who showed primary skin infiltrates within the area affected by herpes simplex. After effective therapy with aciclovir, papules and plaques developed at the site of the herpetic scars. Histologic investigation confirmed dense B-lymphocytic infiltrates with immunoglobulin light chain restriction and a granulomatous reaction. Although the chemotherapeutical regiment was modified, the patient died one month later of a lethal blast crisis. The occurrence of so called isotopic skin reactions and their prognostic significance is discussed.

Blast Crisis↗