[Show abstract][Hide abstract] ABSTRACT: Fixed drug eruption is a fairly common drug-induced hypersensitivity reaction of the skin and the mucous membranes, which is characterized by the re-occurrence of the lesion(s) exactly on the previously involved sites after repeated administration. The pathogenetic mechanisms of this site-specificity are not fully elucidated.
We report on three cases of fixed drug eruption, including a non-pigmenting generalized bullous fixed drug eruption, caused by mefenamic acid in its pure form.
Provocation tests with the assumed causative drug represent the gold standard for establishing the diagnosis and for identifying the culprit. Advantages and pitfalls of topical and systemic provocation tests as diagnostic approaches are discussed.
Journal der Deutschen Dermatologischen Gesellschaft 03/2011; 9(5):374-8. DOI:10.1111/j.1610-0387.2011.07621.x · 1.40 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Activation of skin keratinocytes followed by their apoptotic death leads to eczema and spongiosis formations in patients with atopic dermatitis (AD). TNF-like weak inducer of apoptosis (TWEAK) binds to its receptor, fibroblast growth factor-inducible 14 (Fn14), and controls many cellular activities, including proliferation, migration, differentiation, apoptosis, angiogenesis, and inflammation.
The aim of the study was to investigate the role of TWEAK and Fn14 in the formation of eczema in patients with AD.
Primary keratinocytes were isolated from nonlesional skin from patients with AD and psoriasis and from normal skin of healthy donors. Apoptosis analysis was performed by using annexin V/7-aminoactinomycin D and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling staining. The expression and regulation of TWEAK, TNF-α, Fn14, TNF receptor (TNFR) 1, and TNFR2 were measured by means of RT-PCR, flow cytometric analysis, and ELISA. TWEAK and Fn14 expression of lesional AD and psoriatic skin and normal control skin was analyzed by using immunohistochemistry and immunofluorescence.
TWEAK and TNF-α cooperate in the induction of apoptosis in primary keratinocytes obtained from patients with AD, patients with psoriasis, and healthy subjects and in artificial skin equivalents. TNFR1 and Fn14 were the main receptors involved. TWEAK upregulates TNF-α expression in primary keratinocytes, whereas TNF-α did not affect the expression of TWEAK and its receptors. High TWEAK expression was observed in AD lesions but not in psoriatic lesions or normal skin. Fn14 was highly expressed in the lesional skin of patients with AD and patients with psoriasis and in healthy control skin.
The high expression of TWEAK in lesional AD skin contributes to the difference in keratinocyte apoptosis and lesional formation between AD and psoriasis.
The Journal of allergy and clinical immunology 01/2011; 127(1):200-7, 207.e1-10. DOI:10.1016/j.jaci.2010.11.005 · 11.25 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Keratinocyte (KC) apoptosis is an important mechanism of eczema and spongiosis in patients with atopic dermatitis (AD) and is mediated by IFN-gamma, which is secreted by T(H)1 cells. IL-32 is a proinflammatory cytokine that is involved in the inflammatory processes of rheumatoid arthritis, chronic obstructive pulmonary disease, and Crohn disease. Recently, it was shown that upregulation of IL-32 induces apoptosis.
The aim of the study was to investigate the expression and function of IL-32 in patients with AD.
The expression of IL-32 in KCs was analyzed by means of RT-PCR, ELISA, and flow cytometry. Transfections of small interfering RNA were performed in primary KCs, and apoptosis was analyzed by means of terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling, annexin-V, and 7-amino actinomycin D stainings. Immunofluorescence stainings were used to detect IL-32 in skin biopsy specimens, and serum levels of IL-32 were analyzed by means of ELISA.
We report that IL-32 is expressed in human primary KCs on stimulation with IFN-gamma, TNF-alpha, and T(H)1 cells in contrast to T(H)2, regulatory T (Treg), or T(H)17 cells, which showed no effect. Transfection of primary KCs and artificial skin equivalents with small interfering RNA to IL-32, which resulted in a clear decrease in IL-32 expression, significantly reduced KC apoptosis. Immunofluorescence staining demonstrated that IL-32 was expressed in AD lesional skin, whereas it was present in neither skin biopsy specimens from healthy donors nor in lesional skin from patients with psoriasis. Serum levels of IL-32 from patients with AD correlated with disease severity, but increased serum levels of IL-32 were also detected in asthmatic patients.
The present study demonstrates KCs as a source of IL-32, which modulates KC apoptosis and contributes to the pathophysiology of AD.
The Journal of allergy and clinical immunology 03/2010; 125(4):858-865.e10. DOI:10.1016/j.jaci.2010.01.016 · 11.25 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Allergic diseases represent a major health problem in Europe. They are increasing in prevalence, severity and costs. GA2LEN (Global Allergy and Asthma European Network), an FP6 Network of Excellence, was created in 2005 as a vehicle to ensure excellence in research bringing together research and clinical institutions to combat fragmentation in the European research area and to tackle allergy as a whole. GA2LEN benefited greatly from the voluntary efforts of researchers who are strongly committed to this model of pan-European collaboration. The network was organized in order to increase networking for scientific projects in allergy and asthma around Europe and to make GA2LEN the world leader in the field. Besides these activities, research has been jointly made and the first papers are being published. GA2LEN achievements in general can be grouped as those for a durable infrastructure built up during the project phase those which are project-related work based on these novel infrastructures, and the development and implementations of guidelines. The major achievements of GA2LEN are reported in this paper.
Wiener klinische Wochenschrift 01/2009; 121(17-18):589-97. DOI:10.1007/s00508-009-1246-z · 0.79 Impact Factor