Subject(s)
Diagnostic Techniques, Urological , Medical History Taking/methods , Physical Therapy Modalities , Urinary Bladder , Urinary Incontinence , Cholinergic Antagonists/administration & dosage , Cholinergic Antagonists/adverse effects , Disease Management , Evidence-Based Medicine , Female , Humans , Patient Education as Topic , Physical Examination/methods , Referral and Consultation , Urinary Bladder/pathology , Urinary Bladder/physiopathology , Urinary Incontinence/classification , Urinary Incontinence/diagnosis , Urinary Incontinence/physiopathology , Urinary Incontinence/therapyABSTRACT
Psoriasis is initiated and maintained through a multifaceted interplay between keratinocytes, blood vessels, gene expression, and the immune system. One previous psoriasis model demonstrated that overexpression of the angiopoietin receptor Tie2 in endothelial cells and keratinocytes led to the development of a psoriasiform phenotype; however, the etiological significance of overexpression in each cell type alone was unclear. We have now engineered two new mouse models whereby Tie2 expression is confined to either endothelial cells or keratinocytes. Both lines of mice have significant increases in dermal vasculature but only the KC-Tie2-overexpressing mice developed a cutaneous psoriasiform phenotype. These mice spontaneously developed characteristic hallmarks of human psoriasis, including extensive acanthosis, increases in dermal CD4(+) T cells, infiltrating epidermal CD8(+) T cells, dermal dendritic cells and macrophages, and increased expression of cytokines and chemokines associated with psoriasis, including interferon-gamma, tumor necrosis factor-alpha, and interleukins 1alpha, 6, 12, 22, 23, and 17. Host-defense molecules, cathelicidin, beta-defensin, and S100A8/A9, were also up-regulated in the hyperproliferative skin. All of the phenotypic traits were completely reversed without any scarring following repression of the transgene and were significantly improved following treatment with the anti-psoriasis systemic therapeutic, cyclosporin A. Therefore, confining Tie2 overexpression solely to keratinocytes results in a mouse model that meets the clinical, histological, immunophenotypic, biochemical, and pharmacological criteria required for an animal model of human psoriasis.
Subject(s)
Disease Models, Animal , Endothelial Cells/metabolism , Keratinocytes/metabolism , Psoriasis/genetics , Receptor, TIE-2/genetics , Animals , Blotting, Western , Gene Expression , Gene Expression Profiling , Humans , Mice , Mice, Transgenic , Neovascularization, Pathologic/genetics , Neovascularization, Pathologic/metabolism , Neovascularization, Pathologic/pathology , Oligonucleotide Array Sequence Analysis , Phenotype , Psoriasis/metabolism , Psoriasis/pathology , Receptor, TIE-2/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Skin/blood supply , Skin/metabolism , Skin/pathology , Vascular Endothelial Growth Factor A/biosynthesisABSTRACT
A 39-year-old woman presented with pruritic eczematous plaques on her face, neck, and right hand that she had had for approximately 2 months, following an abrasive injury caused by the deployment of an airbag in a car accident. Results of patch testing were positive for several medicaments and propylene glycol (PG). The patient's condition cleared after discontinuation of all topical products containing PG and her other identified allergens, but she noted flares of her contact dermatitis following the ingestion of foods containing PG. A subset of patients will have a recurrence of dermatitis after the ingestion of a contact sensitizer. Recurrent dermatitis despite complete avoidance of identified topical allergens and a history of recurrent eczema at the patch-test site are clues to the diagnosis of systemic contact dermatitis. Even weak patch reactions to PG, if they persist to a day-7 reading, should be considered potentially relevant. Avoidance of dietary PG includes attention to labels on food and medication and the avoidance of certain foods in restaurants when ingredients cannot be verified.
Subject(s)
Cosmetics/adverse effects , Dermatitis, Allergic Contact/etiology , Dermatologic Agents/adverse effects , Food/adverse effects , Propylene Glycol/adverse effects , Adult , Dermatitis, Allergic Contact/diagnosis , Erythema/drug therapy , Female , Humans , Patch Tests , Recurrence , Skin/pathologyABSTRACT
BACKGROUND: A 64-year-old woman presented with erythematous plaques, tender nodules, and pustules of the dorsal right hand and both legs following long-term treatment with systemic steroids and infliximab. Skin biopsy demonstrated dermal inflammation with foci of necrosis and multinucleated giant cells containing fungal spores. Tissue culture grew Trichophyton rubrum. OBJECTIVE: To report a case that demonstrates the pathophysiology of invasive T. rubrum infection, the mechanisms of action and uses of tumor necrosis factor alpha (TNF-alpha)-inhibiting drugs, and how these drugs may increase patients' risk of invasive dermatophytosis. CONCLUSION: Dermatophytes such as T. rubrum rarely cause invasive disease. This unusual presentation of invasive T. rubrum occurred with immunosuppression by infliximab and systemic steroids. Patients should have a thorough examination for signs of latent infection before TNF-alpha inhibitors are prescribed, including inspection of the skin and nails for signs of dermatophytosis.
