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Biomedical subjects

A Wollenberg

Publications and source records attributed to A Wollenberg.

At least 37 records · Page 2Linked to original sources
PubMed2000

Safety and efficacy of 1 year of tacrolimus ointment monotherapy in adults with atopic dermatitis. The European Tacrolimus Ointment Study Group.

OBJECTIVE: To investigate the safety and efficacy of using 0.1% tacrolimus ointment for long-term treatment of atopic dermatitis. DESIGN: Open-label, noncomparative study with 6 to 12 months of follow-up. SETTINGS: Outpatient departments in 30 study centers in 11 European countries. PATIENTS: We enrolled 316 patients aged 18 years and older with moderate to severe atopic dermatitis, 200 for 6 months and 116 for 12 months; 77.5% of patients completed the study. INTERVENTION: Twice-daily application of 0.1% tacrolimus ointment on all affected skin. Visits were scheduled on day 1; after 1, 2, and 4 weeks of treatment; and monthly thereafter. MAIN OUTCOME MEASURES: Safety assessments included monitoring of adverse events, clinical laboratory values, and tacrolimus blood concentrations. Efficacy end points included a combined score (modified Eczema Area and Severity Index) and an investigator's global assessment. RESULTS: Local irritation, adverse events such as burning sensation (47% of patients), pruritus (24% of patients), and erythema (12% of patients) were common but tended to occur only when initiating treatment. Laboratory values showed no marked changes over time. Systemic absorption was minimal, with the maximum tacrolimus blood concentration being less than 1 ng/mL in 76% of patients. All efficacy end points showed improvement. The mean (SD) modified Eczema Area and Severity Index score was 23.7 (12.6) at day 1, 13.5 (11.3) at week 1, 6.1 (9.2) at month 6, and 6.1 (8.1) at month 12. Marked or excellent improvement or clearance of disease was reported in 54%, 81%, and 86% of patients at week 1, month 6, and month 12, respectively. CONCLUSION: Up to 1 year of tacrolimus ointment use was safe and effective in patients with atopic dermatitis. Arch Dermatol. 2000;136:999-1006

Administration, Topical↗
PubMed2000

[Immunosuppressive macrolides and their use in dermatology].

The immunosuppressive macrolides are a novel class of antiinflammatory substances, which could supplant glucocorticosteroids for the topical treatment of some chronic inflammatory skin diseases. Cyclosporine A (CyA), well known from transplantation medicine for years, is licensed in Germany for oral treatment of psoriasis and atopic dermatitis but is not suitable for topical therapy. Tacrolimus (FK506) penetrates the inflamed epidermis and is regarded as the key immunosuppressive macrolide. Clinical trials have demonstrated the efficacy of FK506 ointment for atopic dermatitis, many case reports have been published regarding other inflammatory skin diseases. The ascomycin derivative ASM 981 has many of the properties of FK506 but less data is available at present. Sirolimus (Rapamycin) is structurally related to FK506 but has other biological effects since its molecular actions involve different biochemical pathways. A review of the biochemical and cellular properties, mode of action, therapeutic efficacy and unwanted side effects, as well as data from clinical trials and status of licensing, is given for the respective drugs.

Administration, Topical↗
PubMed2000

Phenotyping of epidermal dendritic cells allows the differentiation between extrinsic and intrinsic forms of atopic dermatitis.

UNLABELLED: Atopic dermatitis (AD) is a clinically characteristic, chronic inflammatory skin disease of unknown origin. IgE-mediated uptake and antigen focusing of environmental allergens by dendritic cells (DCs) is assumed to be a central immunopathogenetic event. A so-called intrinsic type of AD (IAD) has been delineated from the more common extrinsic AD (EAD) by normal serum IgE levels, negative RAST tests and negative immediate-type skin reactions towards environmental allergens. The recently characterized human autoantigen Hom S 1 has been proposed to play a part in the pathogenesis of IAD. OBJECTIVES: To compare clinical and laboratory data between patients with IAD and EAD, and to investigate potential differences in the inflammatory micromilieu of the epidermal compartment in IAD and EAD lesions. METHODS: Epidermal DC phenotyping, a recently validated technique based on the three-colour flow cytometric analysis of Langerhans cells and the so-called inflammatory dendritic epidermal cells from epidermal single-cell suspensions, was performed on samples from 69 patients with AD (seven with IAD and 62 with EAD) and 94 controls. RESULTS: Patients with EAD tended to have an earlier onset of disease but similar disease duration and family history of atopic diseases. Quantitative analysis of CD36 expression on DCs as a marker of inflammation, as well as the percentage of inflammatory dendritic epidermal cells in the CD1a+ epidermal DC pool, indicated a comparable disease activity in IAD and EAD. EAD was characterized by a significantly higher FcepsilonRI expression on the CD1a+ epidermal DCs than IAD. Using the FcepsilonRI/FcgammaRII expression ratio as a disease marker for AD, values for IAD fell below the diagnostic cut-off level of 1.5 for this ratio. CONCLUSIONS: While IAD is clinically similar to EAD, the inflammatory microenvironment in this condition seems different from classical EAD and can be distinguished by phenotyping of epidermal DCs.

Adolescent↗
PubMed2000

Atopic dermatitis: pathogenetic mechanisms.

Atopic dermatitis (AD) is a chronic inflammatory skin disease with increasing incidence and socio-economical relevance. The diagnosis is made on clinical grounds and different diagnostic criteria sets have been established. The majority of all AD cases is associated with a sensitization to environmental allergens and increased serum IgE (so-called extrinsic AD), but about 10--30% of all cases suffer from the so-called intrinsic AD, which obviously lacks any link to the classical atopic diathesis. The genetic background of AD has been investigated by target gene approach by different groups with mostly contradictory results for each of the genes under study. An imbalance in the spectrum of Th1/Th2 responses, a disturbed prostaglandin metabolism, intrinsic defects in keratinocyte function, delayed eosinophil apoptosis, IgE-mediated facilitated antigen presentation by epidermal dendritic cells, a two phase model of the inflammatory response and staphylococcal superantigen effects are among the currently studied pathogenetical aspects of extrinsic AD, which are reviewed in this paper.

Dermatitis, Atopic↗
PubMed1999

Phenotyping of epidermal dendritic cells: clinical applications of a flow cytometric micromethod.

BACKGROUND: The differential diagnosis of inflammatory skin diseases is largely based on the patient's history and the morphological analysis of the skin lesion. Laboratory data, such as serum IgE-level and prick and patch tests, may be helpful but do not assess individual lesions. The assumption of our approach is that each individual lesion is associated with a specific microenvironment and that the immunophenotype of the two epidermal dendritic cell populations, Langerhans cells (LC) and inflammatory dendritic epidermal cells (IDEC), reflects this environment in a disease-specific manner. METHODS: A flow cytometric micromethod was developed to directly analyze individual inflammatory human skin lesions. Crude epidermal single cell suspensions were prepared by trypsinization, stained for three-color analysis with different monoclonal antibodies and the vital stain 7-amino-actinomycin-D, and finally analyzed on a single laser equipped FACScan flow cytometer. RESULTS: With a limited set of cell surface markers, such as FcepsilonRI, FcgammaRII/CD32, CD1b and CD36, highly specific diagnostic criteria for atopic dermatitis and inflamed human skin could be established. CONCLUSIONS: Phenotyping of epidermal dendritic cells is a useful procedure helpful in differential diagnosis of inflammatory skin diseases.

Antigens, CD1↗
PubMed1998

IL-10 inhibits ICAM-1 expression on human Langerhans cells but not on keratinocytes, dermal endothelial cells or fibroblasts.

Intercellular adhesion molecule-1 (ICAM-1) is regularly expressed or inducible on all major cutaneous cell populations including Langerhans cells, keratinocytes, endothelial cells and dermal fibroblasts. ICAM-1 is induced in the skin under inflammatory conditions and plays an important role in the activation of T cells. Interleukin-10 (IL-10) is a pluripotent immunosuppressive cytokine that inhibits proliferation of T cells via inhibition of antigen-presenting cells including Langerhans cells. We demonstrates that IL-10 inhibits baseline and also cytokine-stimulated ICAM-1 expression on human Langerhans cells, which has previously been shown in the murine system. No effect of IL-10 was seen on human dermal vascular endothelial cells, which like Langerhans cells are also able to present antigen. Additionally, no inhibitory effect of IL-10 was observed on the ICAM-1 expression of keratinocytes and dermal fibroblasts. As IL-10 only weakly suppresses MCH II on human Langerhans cells, inhibition of ICAM-1 and other accessory molecules by IL-10 seems to be an important mechanism inhibiting the antigen-presenting function of human Langerhans cells.

Dermis↗
PubMed1998

Aquarium dermatitis: cercarial dermatitis in an aquarist.

A 33-year-old man presented with very itchy red papules on the back of his hands and forearms. These papules appeared about 90 min after he had cleaned his aquarium in which he kept native fish and watersnails. He had obtained the watersnails some weeks before from a nearby pond. Examination of water from the aquarium revealed cercariae. The clinical diagnosis of cercarial dermatitis was corroborated. Cercarial dermatitis has repeatedly been seen in swimmers but not in aquarists keeping fish in a home aquarium.

Adult↗
PubMed1997

[Dorfman-Chanarin syndrome--a neutral lipid storage disease].

Dorfman-Chanarin syndrome is a rare, autosomal recessive inherited lipid storage disease with skin manifestations in form of congenital ichthyotic erythroderma. Demonstration of lipid vacuoles in neutrophils from peripherals blood smears in patients with ichthyotic erythroderma leads to the diagnosis. Other organ systems, such as CNS, liver, muscle, ears and eyes, are frequently involved. Since Dorfman-Chanarin syndrome may present with just skin findings, it should be included in the differential diagnosis of the congenital ichthyoses. Microscopic examination of peripheral blood smears is recommended in all patients with ichthyosis. We summarize the current data on the pathogenesis, diagnosis, differential diagnosis, and therapeutic options in Dorfman-Chanarin syndrome, give an overview of the clinical manifestations of the 23 patients affected with this rare disease.

Adolescent↗
PubMed1997

Chronic ulcerative stomatitis.

Chronic ulcerative stomatitis (CUS) has recently been described as a new disease entity characterized by chronic ulceration of oral mucosa which responds to treatment with hydroxychloroquine. It has a particular type of stratified epithelium-specific, antinuclear autoantibody as an immunological marker. Twelve cases have been reported in the literature. We present a 40-year-old woman with an 11-year history of chronic oral ulcerations. Other dermatological diseases, including oral lichen planus, pemphigus vulgaris and cicatricial pemphigoid, as well as bullous lupus erythematosus, were excluded. The clinical diagnosis of CUS was confirmed on the grounds of the immunological and ultrastructural findings. The lesions initially responded to high doses of systemic corticosteroids but relapsed promptly after dose reduction. Dapsone was ineffective. Hydroxychloroquine, given at a dosage of 200-400 mg/day, led to a complete and long-lasting remission.

Adult↗
PubMed1997

Urticaria haemorrhagica profunda.

Substantial subcutaneous haemorrhage without preceding trauma or underlying bleeding disorder is a rare occurrence in dermatological practice, essentially restricted to early childhood (acute haemorrhagic oedema of childhood). We report an adolescent with a morphologically unique bleeding manifestation. A 16-year-old boy presented with two episodes of massive subcutaneous haemorrhage in association with urticarial vasculitis. There was no history of preceding trauma or haemorrhagic disorder. Haemorrhage was observed in areas typically affected by angioedema, such as the periorbital, perioral, lingual, sublingual and laryngeal areas. History revealed an atopic diathesis with hay fever and examination showed alopecia areata. An antinuclear antibody titre and the presence of lupus anticoagulant indicated transient antiphospholipid antibodies. As urticaria corresponds to urticaria profunda angioedema, we hypothesize a pathophysiological relationship between superficial urticarial vasculitis and the deep variant of urticarial vasculitic disease, leading to the unique morphology present in our patient.

Adolescent↗
PubMed1997

Acne conglobata and Klinefelter's syndrome.

Acne conglobata has been reported to be more common and more severe in XYY chromosomal aberration than in normal subjects. Whereas only exceptional cases have been observed in the more common XXY Klinefelter karyotype. We report a 17-year-old male with both Klinefelter's syndrome and acne conglobata, spreading from face to upper arms, trunk, buttocks and upper legs. The serum level of testosterone was normal, whereas luteinizing hormone and follicle-stimulating hormone were elevated. Skin lesions responded well to a combined therapeutic regimen including oral isotretinoin and prednisolone. An overview of severe acne in relation to chromosomal abnormalities is given and diagnostic and therapeutic options discussed.

Acne Vulgaris↗
PubMed1996

New insights in the structure and biology of the high affinity receptor for IgE (Fc epsilon RI) on human epidermal Langerhans cells.

The recent structural and functional analysis of the high affinity receptor for IgE (Fc epsilon RI) expressed on human epidermal Langerhans cells (LC) revealed new aspects of the biology of this structure. In contrast to basophils and mast cells where this receptor seems to be expressed constitutively at a constant level, the expression of Fc epsilon RI on LC varies on the donor and the inflammatory environment of the cells and lacks the classical beta-chain. This also implies functional differences most probably related to the expression level. Although the signalling pathway seems to be similar to that of basophils or mast cells, LC from individuals with atopic dermatitis are fully activated by receptor ligation while LC from normal individuals fail to exhibit calcium mobilization under the same conditions. Finally, LC from normal and atopic individuals use Fc epsilon RI to maximize antigen uptake via specific IgE and subsequent presentation to T cells. Thus, Fc epsilon RI expressed on LC differs in terms of structure and function from that expressed on effector cells of anaphylaxis.

Antigen Presentation↗
PubMed1996

Immunomorphological and ultrastructural characterization of Langerhans cells and a novel, inflammatory dendritic epidermal cell (IDEC) population in lesional skin of atopic eczema.

We investigated epidermal cell suspensions prepared from lesional and nonlesional atopic eczema skin, other inflammatory skin conditions, and normal human skin for high-affinity IgE receptor (Fc epsilon RI) expression on dendritic CD1a cells by quantitative flow cytometric analysis. A single CD1a bright/CD1b neg/Fc epsilon RI dim/CD23 neg/CD32 dim/HLA-DR bright/CD36 neg population was found in normal skin. In contrast, lesional skin of atopic eczema and other inflammatory skin diseases harbored variable proportions of two distinct CD1a populations. Both populations exhibited typical ultrastructural features of Langerhans cells, but the second one lacked Birbeck granules and was unreactive to the Birbeck granule-specific LAG antibody. Both populations differed phenotypically: classical Langerhans cells were CD1a bright/CD1b neg/Fc epsilon RI dim/CD23 neg/CD32 dim/HLA-DR bright/CD36 dim, while the second population was CD1a dim/CD1b dim/Fc epsilon RI bright/CD23 dim/CD32 dim/HLA-DR bright/CD36 bright. The highest Fc epsilon RI expression was found on the second CD1a population in lesional atopic eczema skin. Furthermore, Fc epsilon RI expression on CD1a cells correlated significantly with the serum IgE level of the patients. Thus, a distinct population of CD1a inflammatory dendritic epidermal cells different from classical Langerhans cells appears in the epidermis of lesional skin and is subjected to specific signals leading to the upregulation of Fc epsilon RI in atopic eczema skin.

Antigens, CD1↗