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Biomedical subjects

H Hönigsmann

Publications and source records attributed to H Hönigsmann.

At least 55 records · Page 3Linked to original sources

Generalized pustular psoriasis of pregnancy (impetigo herpetiformis).

A 17-year-old woman had a sudden eruption of pustules in her intertriginous areas as well as of erythematosquamous plaques on the scalp, elbows, palms and soles in the third trimester of her first pregnancy. Histopathological evaluation of a biopsy revealed typical changes of pustular psoriasis with parakeratosis and abscesses of neutrophils (Kogoj's spongiform pustules). The diagnosis of pustular psoriasis was established by the typical clinical and histopathological findings. Laboratory parameters showed a highly elevated blood sedimentation rate, hypoferric anemia and decreased albumin levels. Serum concentrations of parathormone and its metabolites were normal. After systemic treatment with glucocorticosteroids and antibiotics, the lesions improved but did not clear. After delivery of a healthy boy, therapy was switched to retinoid photochemotherapy with isotretinoin and PUVA that resulted in rapid and complete clearing of the eruption. The coincidence of plaque-type psoriasis and a pustular eruption as described previously in impetigo herpetiformis supports the view that this dermatosis of pregnancy is a variant of generalized pustular psoriasis.

Dermatitis Herpetiformis↗

Successful use of extracorporeal photochemotherapy in the treatment of severe acute and chronic graft-versus-host disease.

Extracorporeal exposure of peripheral blood mononuclear cells to the photosensitizing compound 8-methoxypsoralen and ultraviolet A radiation has been shown to be effective in the treatment of several T-cell-mediated diseases, including cutaneous T-cell lymphoma and rejection after organ transplantation. We present 21 patients (10 men and 11 women) with hematological malignancies with a median age of 36 years (range, 25 to 55 years) who had received marrow grafts from sibling (n = 12) or unrelated (n = 9) donors. Six patients had acute graft-versus-host disease (GVHD) grade II to III not responding to cyclosporine A (CSA) and prednisolone when referred to extracorporeal photochemotherapy (ECP). In 15 patients, 2 to 24 months after bone marrow transplantation (BMT), extensive chronic GVHD with involvement of skin (n = 15), liver (n = 10), oral mucosa (n = 11), ocular glands (n = 6), and thrombocytopenia (n = 3) developed and was unresponsive to conventional therapy, including steroids. All patients were treated with ECP on 2 consecutive days every 2 weeks for the first 3 months and thereafter every 4 weeks until resolution of GVHD. ECP was tolerated excellently without any significant side effects. After a median of 14 cycles of ECP, acute GVHD resolved completely in 4 of 6 patients (67%) and partially in another 2 patients. Cutaneous chronic GVHD completely resolved in 12 of 15 (80%) patients. Contractures of knees and elbows due to scleroderma resolved partially. Oral mucosal ulcerations resolved in all patients. Seven of 10 patients (70%) with liver involvement had complete responses after ECP. After discontinuation of ECP, no severe infections were observed. Our findings suggest that ECP is a safe and effective adjunct therapy for both acute and extensive chronic GVHD with skin and visceral involvement and resistance to conventional therapy.

Acute Disease↗

Flow cytometric quantification of UV-induced cell death in a human squamous cell carcinoma-derived cell line: dose and kinetic studies.

Exposure to ultraviolet (UV) radiation and photochemotherapy induces apoptotic cell death in epidermal cells. In this study annexin V binding and propidium iodide (PI) uptake have been measured by flow cytometry to evaluate UV-induced cell death in the human squamous cell carcinoma-derived cell line A 431. Physiological and therapeutical relevant doses of UVA, UVA1, UVB, narrow-band UVB (311 nm) and photochemotherapy using 100 ng/ml of 8-methoxypsoralen (8-MOP) with UVA or UVA1 (PUVA or PUVA1) have been applied. Doses ranged from 8 to 96 J/cm2 for UVA1 and UVA, from 8 to 128 mJ/cm2 for UVB, from 256 to 4096 mJ/cm2 for narrow-band UVB (311 nm) and from 1 to 16J/cm2 for photochemotherapy. Results show that the amount of annexin V binding, a measure of early apoptosis, as well as PI uptake, a parameter of ultimate cell death, are strictly correlated with the applied UV dose. Peak values of annexin V-positive cells are noted 12 h after UV exposure in all protocols and are followed by an increase of PI-uptaking cells with peak values at 24 h after UVA and UVA1, and 48 h after PUVA, PUVA1, UVB and narrow-band UVB. To compare the effect of different wavelengths and light sources, dose equivalents are calculated based on the induction of 50% cell death (as determined by PI uptake). The equivalents are 96 J/cm2 for UVA and UVA1, 16 J/cm2 for PUVA and PUVA1, 256 mJ/cm2 for UVB and 2048 mJ/cm2 for narrow-band UVB. Our results establish annexin V/PI double staining as an appropriate method for the quantification of UV-induced cell death. Moreover, they provide a basis for further investigations concerning mechanisms and modifications of UV-induced apoptosis.

Annexin A5↗

Linear focal elastosis (elastotic striae): increased number of elastic fibres determined by a video measuring system.

We present an unusual case of linear focal elastosis occurring exclusively on the legs of a 13-year-old girl. An increase of elastic fibres (EF) was demonstrated histologically, and the number of EF in lesional and normal skin was quantified using a video measuring system. EF were found to be increased by about 100% in lesional skin compared with unaffected skin. EF were elongated, thinned and split at their ends with a paintbrush formation.

Adolescent↗

Stress proteins in the cellular response to ultraviolet radiation.

Virtually all cells-from prokaryotes to highly differentiated mammalian tissues-respond to a sudden increase in temperature with increased production of a limited set of proteins, called heat shock proteins or stress proteins (hsp). Other stress factors such as alcohol, heavy metals, oxidants and agents leading to protein denaturation are equally able to induce a similar response. Induction of hsp is followed by a transient state of increased resistance to further stress. Many hsp function as "molecular chaperones" by binding to partially folded or misfolded proteins thus preventing their irreversible denaturation during stress exposure. The high evolutionary conservation of this reaction suggests its importance for the survival of cells and tissues under hostile environment conditions. Ultraviolet radiation (UV) exerts many potentially harmful effects on prokaryotic and eukaryotic cells and hsp may help the cell to cope with UV-induced damage. This review will focus on the role of hsp in the cellular response of mammalian skin to UV. Hsp have been detected in resting as well as stress exposed epidermal and dermal cells and experimental evidence points to the fact that these proteins mediate protection from UV induced cell death in vitro and in vivo. Experimental studies further indicate that UV itself might be able to induce the expression of specific hsp. Thus, hsp might provide an adaptive cellular response to increasing exposure to UV. Furthermore, UV-activation of hsp synthesis may provide a valuable model for investigation of the transcription regulation of UV-induced gene expression.

Heat-Shock Proteins↗

Skin tumors in photochemotherapy for psoriasis: a single-center follow-up of 496 patients.

BACKGROUND: The significance of oral psoralen photochemotherapy (PUVA) for the development of nonmelanoma skin cancers (NMSC) is still controversial. OBJECTIVE: We evaluated 496 psoriatics, who received PUVA treatment according to the European PUVA protocol in order to reassess the influence of the cumulative UVA dose on the development of NMSC and to answer the question if there is a UVA threshold dose above which the carcinogenic risk is increased. METHODS: The study was conducted as a retrospective investigation. All patients were seen personally. Age, sex, skin type, cumulative UVA dose and carcinogenic risk factors (arsenic, X-rays, tar, UVB, methotrexate) were recorded and investigated by marginal (MA) and partial effects analyses (PA) according to the Cox regression model. RESULTS: In 14 patients (2.8%), one or multiple histologically confirmed NMSC were diagnosed. Nine patients (1.8%) had squamous cell carcinoma (SCC), 5 patients (1.0%) had basal cell carcinoma (BCC). No patient had both types of NMSC. None of the SCC had metastasized. By taking the appearance of BCC and SCC as the endpoint, arsenic [MA: relative risk (RR) = 7.62; PA:RR = 5.36], tar (MA:RR = 4.51; PA:RR = 3.83) and methotrexate (MTX; MA:RR = 4.97; PA:RR = 4.07) appear to produce strong and significant effects (p < 0.05), both in MA and PA. Using the endpoint SCC only, the effect of the natural logarithm of UVA (ln UVA; RR = 2.47), arsenic (RR = 11.2), tar (RR = 9.92) and MTX (RR = 7.1) is significant (p < 0.05) in MA. In PA, only the effect of arsenic (RR = 5.19) is strong and significant (p < 0.05) while the effects of tar (RR = 7.85), MTX (RR = 3.22) and ln UVA (RR = 2.77) are strong but of borderline significance (p = 0.05-0.11). Nonlinear effects of ln UVA on the risk of SCC were far from significant (p > 0.2). CONCLUSION: PUVA with the European treatment protocol appears to be only a weak carcinogen by itself for SCC with a linear increase in tumor risk but not for BCC development.

Administration, Oral↗

Bullous pemphigoid induced by PUVA therapy.

An 80-year-old psoriatic patient developed a blistering eruption during oral PUVA therapy. The diagnosis of bullous pemphigoid (BP) was established by routine histopathology, which demonstrated subepidermal blistering, and direct immunofluorescence, which revealed linear deposits of IgG, IgM and C3 along the basement membrane zone. Indirect immunofluorescence using normal human split skin revealed binding of IgG antibodies to the epidermal side, thus confirming a subepidermal blistering disorder. These proteins were identified by the immunoblotting technique as BP antigens I and II. Clinically, the lesions could be reproduced by phototesting using topical 8-methoxypsoralen. Again, the histopathological and immunopathological findings were consistent with the diagnosis of PUVA-induced BP. To the best of our knowledge, this is the first report demonstrating psoriasis-associated BP, in which the clinical diagnosis of BP is confirmed by immunoblotting analysis. The exact role of UV light in precipitating bullous lesions, particularly the question whether UV light may represent an unspecific epidermal injury leading to further attraction of autoantibodies to the basement membrane zone, as suggested recently by an experimental study in rodents, remains to be clarified in future studies.

Aged↗

Photodynamic therapy of epithelial skin tumours using delta-aminolaevulinic acid and desferrioxamine.

Photodynamic therapy (PDT) uses photosensitizing drugs, such as porphyrins, and light for cancer treatment. In the present clinical study we employed topical application of the porphyrin precursor delta-aminolaevulinic acid (ALA) in combination with desferrioxamine (df) for the induction of endogenous porphyrin synthesis. Irradiation was performed with a light source consisting of a halogen lamp with a red filter and a fibreoptic device. Irradiances ranged from 50 to 300 mW/cm2. We treated 49 patients with this PDT regimen. In 32 patients we treated a total of 34 superficial basal cell carcinomas (BCCs) and 22 nodular BCCs, in nine patients 43 solar keratoses, and in eight patients 10 lesions of Bowen's disease. After a single treatment, 30 (88.2%) of the superficial and seven (31.8%) of the nodular BCCs, 35 of 43 (81.4%) solar keratoses, and three (30%) of the Bowen's disease lesions showed complete remission. The post-treatment observation period was up to 20 months. Repeat therapy was required in six nodular and four superficial BCCs. Biopsies were obtained before treatment, and at variable intervals after treatment. Topical PDT of skin tumours with ALA-df-induced porphyrins is effective in the management of epithelial skin tumours.

Aminolevulinic Acid↗

Ultraviolet radiation for treatment of cutaneous T-cell lymphoma.

Cutaneous T-cell lymphoma (CTCL) often begins as limited patches and plaques on the skin that can be effectively treated with ultraviolet radiation. Many long-term remissions and cures have been well documented with the use of ultraviolet radiation alone for stage I CTCL. The side effects of this treatment are minimal.

Combined Modality Therapy↗

Safety and effectiveness of an aggressive and individualized bath-PUVA regimen in the treatment of psoriasis.

BACKGROUND: The optimal therapeutic regimen of bath-PUVA therapy of psoriasis is still under debate. OBJECTIVE: We investigated the safety and efficacy of an aggressive and individualized bath-PUVA regimen. METHODS: Two closely matched groups of 22 psoriatic patients were treated either with 30-min baths in 0.0003% 8-methoxypsoralen (8-MOP) aqueous solution or oral administration of the drug. According to the standard European regimen, treatments were delivered 4 times a week starting with the minimal phototoxic dose. RESULTS: Complete clearing or marked improvement was observed in all the patients. However, with bath-PUVA, the same therapeutic effect required smaller cumulative UVA doses (39.3 +/- 15.8 vs. 123.8 +/- 39.9 J/cm2) and lower numbers of exposures (15.2 +/- 4.4 vs. 20.6 +/- 4.2). Both differences were significant at the 0.01 level (Student's t test). Gastro-intestinal side-effects were of course restricted to oral 8-MOP. The incidences of burns and pruritus were similar. CONCLUSION: Using an aggressive and individualized schedule, bath-PUVA therapy showed a greater efficacy than oral PUVA therapy while being just as safe.

Administration, Oral↗

Immunohistochemistry of port-wine stains and normal skin with endothelium-specific antibodies PAL-E, anti-ICAM-1, anti-ELAM-1, and anti-factor VIIIrAg.

BACKGROUND AND DESIGN: Immunohistochemical analysis using four monoclonal antibodies specific for endothelium was performed to evaluate the possible role the endothelium may play in the pathogenesis of port-wine stains. In 11 patients with port-wine stains, biopsy specimens were obtained from involved and normal skin. On frozen tissue sections, we studied and compared the distribution and staining pattern of PAL-E, anti-intercellular adhesion molecule-1 (ICAM-1), anti-endothelial leukocyte adhesion molecule-1 (ELAM-1), and anti-factor VIIIrAg (FVIIIrAg), all recognizing specific epitopes of vascular endothelial cells. RESULTS: The PAL-E, anti-FVIIIrAg, and anti-ICAM-1 antibodies showed a similar distribution and staining pattern. The intensity of staining was equally strong with PAL-E and FVIIIrAg, while the expression of ICAM-1 was moderate. The ELAM-1 antibody exhibited only a weak expression in about 70% of evaluated specimens. No substantial differences in the intensity and distribution pattern of expression of these proteins could be demonstrated between normal skin and port-wine stains. CONCLUSION: Our findings suggest that the abnormal vessel pathologic findings in port-wine stains are not due to defects associated with the endothelium. According to PAL-E antibody staining properties, port-wine stain vessels could be classified as capillaries and/or postcapillary venules and small veins.

Adult↗

Comparison of narrow-band (311 nm) UVB and broad-band UVA after oral or bath-water 8-methoxypsoralen in the treatment of psoriasis.

BACKGROUND: There is a disparity between the absorption spectrum of 8-methoxypsoralen and the action spectrum for psoralen-sensitized erythema. In an action spectrum corrected for unsensitized reaction 313 and 365 nm have similar efficacies. OBJECTIVE: We evaluated the relative erythemogenic and antipsoriatic efficacy of narrow-band (311 nm) UVB with and without prior psoralen exposure. We also compared the effects of narrow-band UVB and broad-band UVA after oral and bath-water psoralen exposure. METHODS: Patients with psoriasis underwent half-side comparison studies. In one group the therapeutic efficacy of 311 nm UVB with and without oral psoralen was assessed. The second group received UVA and 311 nm UVB after oral psoralen. The third group was exposed to both radiation sources after bath-water exposure. RESULTS: The erythemogenic, pigmentogenic, and therapeutic efficacy of 311 nm was increased by oral psoralen. With systemic 8-methoxypsoralen, UVA was comparable to 311 nm UVB. After bath-water exposure, 311 nm was clearly superior to broad-band UVA. CONCLUSION: The efficacy of narrow-band 311 nm UVB can be enhanced by psoralen. Narrow-band 311 nm UVB is also effective after psoralen bath-water delivery.

Administration, Cutaneous↗