Human Papillomavirus-type distribution in anogenital lesions of prepubertal children.

BACKGROUND: In contrast to adults, only limited data are available on the human papillomavirus (HPV)-type spectrum in anogenital warts (AGW) of children. OBJECTIVE: This study aimed to evaluate the HPV-type spectrum in AGW of prepubertal children. MATERIALS & METHODS: In a retrospective German multicentre study, HPV genotyping was performed in AGW biopsies of 55 1- to 12-year-old children using HPV group-specific PCRs followed by hybridization with type-specific probes or sequence analysis. RESULTS: Human papillomavirus-DNA was found in 53 of the 55 AGW. In 58.5% (31/53) of the HPV-positive AGW, mucosal HPV types were detected. HPV6 (27/53, 50.9%) was the predominant type. 43.4% (23/53) of the lesions were induced by cutaneous HPV types (HPV2, HPV27, HPV57). Mucosal HPV types were significantly more common in children under 5 years of age than in children 5 years of age and older (22/25, 88.0% [95% CI: 70.0-95.8] vs. 9/28, 32.1% [95% CI: 17.9-50.7], P < 0.001). In contrast, cutaneous HPV types were significantly more prevalent in the 5- to 12-year age group (4/25, 16.0% [95% CI 6.4-34.7] vs. 19/28, 67.9% [95% CI 49.3-82.1], P < 0.001). CONCLUSION: Anogenital warts in 5- to 12-year-old children are frequently associated with cutaneous HPV types, possibly due to horizontal transmission. HPV typing, in addition to comprehensive clinical and psychosocial evaluation, can potentially help in the assessment of these cases.

[Paraneoplastic subacute cutaneous lupus erythematosus]. / Paraneoplastischer subakut kutaner Lupus erythematodes.

Subacute cutaneous lupus erythematosus (SCLE) is a subtype of cutaneous lupus erythematosus characterized by high photosensitivity, the occurrence of annular or papulosquamous skin lesions located in body regions exposed to UV light, the presence of anti-Ro/SS­A antibodies, and mild systemic involvement, such as arthralgia and myalgia. Similar to other subtypes of cutaneous lupus erythematosus, certain trigger factors exist for the development of SCLE, such as exposure to UV light, cigarette smoking and drugs. Rheumatic diseases, such as dermatomyositis, have been known as paraneoplastic syndromes for a long time. In recent years, there has been an accumulation of publications on the association of SCLE with malignant diseases. This article reports the case of a 78-year-old female patient who was diagnosed with the concomitant development of SCLE and gastric carcinoma. In all older patients with SCLE, patients with widespread skin affection outside the UV-exposed body areas or patients with B­symptoms, the presence of a paraneoplastic SCLE should be considered and appropriate diagnostic steps should be initiated to screen for an associated neoplastic disease.

[Reticular erythematous mucinosis-A special subtype of cutaneous lupus erythematosus?] / Retikuläre erythematöse Muzinose ­ Sonderform eines kutanen Lupus erythematodes?

Reticular erythematous mucinosis (REM syndrome) is a rare skin disease that predominantly affects women. It is clinically characterized by flat, partly reticular, irregularly configurated pale erythema located in the region of the central chest and upper back. The skin alterations are usually asymptomatic or associated with slight pruritus or burning. Extracutaneous diseases and involvement of internal organs do not occur in REM syndrome. Histopathological features include perivascular and periadnexal lymphocytic inflammatory infiltrates as well as increased deposition of mucin in the dermis. Due to the similar histology to lupus erythematosus (LE) tumidus, it is discussed whether REM syndrome can be assigned to the spectrum of cutaneous LE or can be assessed as a lupus-like disease. Moreover, both conditions respond well to treatment with hydroxychloroquine.

[Diffuse hyperkeratotic papules of the lower abdomen and genital region in a 38-year old male patient]. / Diffuse hyperkeratotische Papeln am unteren Abdomen und im Genitalbereich bei einem 38­jährigen Patienten.

A patient with diffuse angiokeratomas of the lower abdomen and genital region was diagnosed with Fabry disease on the basis of genetic testing. Fabry disease is an X-linked lysosomal storage disease that can affect several organ systems including the heart or kidneys, resulting in reduced median survival. Pathogenetically, Fabry disease leads to a deficiency of the lysosomal enzyme α­galactosidase A (α-GAL A). Treatment options include lifelong enzyme replacement therapy or chaperone therapy.

CD30-positive primary cutaneous anaplastic large cell lymphoma with coexistent pseudocarcinomatous hyperplasia.

CD30-positive primary cutaneous anaplastic large cell lymphoma (C-ALCL) is an indolent type of cutaneous lymphoma with favourable clinical prognosis. Pseudocarcinomatous hyperplasia (PCH) is a rare benign epithelial condition that can resemble invasive squamous cell carcinoma both clinically and histopathologically. PCH predominantly occurs in CD30-positive lymphoproliferative disorders. We report a 75-year-old woman with PCH in a multifocal C-ALCL located on the scalp and right retroauricular area, which rapidly responded to treatment with psoralen ultraviolet A photochemotherapy. Comprehensive virological analyses for potential oncogenic viruses, including Epstein-Barr virus, human herpesvirus-8, human papillomaviruses, the recently discovered cutavirus and nine different human polyomaviruses, were negative.

[CHIP Germany: Impact of a Lifestyle Coaching Intervention on Nutritional Behaviour Change in Primary and Secondary Prevention of Type 2 Diabetes and the Importance of Social-Cognitive Variables]. / CHIP Deutschland: Einfluss eines Lebensstil-Schulungsprogramms zur Primär- und Sekundärprävention von Typ 2 Diabetes auf das Ernährungsverhalten und die Bedeutung sozialkognitiver Variablen.

Background: A high fibre and moderate fat diet can reduce the metabolic risk in diabetics. This study is the first one to test which social-cognitive variables affect nutritional behaviour changes in an educational lifestyle intervention. Patients and Methods: Subjects with diabetes or at high risk (intervention: N=43; control: N=40) joined an initial and a final individual health-coaching, an 8-week comprehensive lifestyle programme und a 10-month follow-up-period. Beside anthropometric, vital und clinical parameters (e. g., weight, HbA1c, FINDRISK), behavioural stages (preintenders, intenders, actors), outcome-expectancies, action planning and self-efficacy were evaluated for a healthy diet in both groups. Results: Weight, nutritional behaviour, self-efficacy, action planning, and outcome expectancies improved in the intervention group. Improved self-efficacy after the lifestyle programme was linked to weight reduction. Discussion: The metabolic risk profile was reduced by the educational lifestyle programme. A highly developed self-efficacy seems to help to change nutritional behaviour and therefore prevent and deal with diabetes. Conclusion: Behavioural lifestyle-coachings should focus on the volitional phase and implicitly improve self-efficacy.

Glutathione-S-transferase T1 genotyping and phenotyping in psoriasis patients receiving treatment with oral fumaric acid esters.

BACKGROUND: Glutathione S-transferases (GSTs) are involved in detoxification of xenobiotics such as fumaric acid esters (FAE). OBJECTIVES: To perform GSTT1 geno- and phenotyping in psoriasis patients treated with FAE to find out whether the responder status and/or occurrence of side-effects are associated with allelic variants and enzymatic activity of GSTT1. METHODS: We treated 106 psoriasis patients with FAE. GSTT1 genotyping was performed using PCR, phenotyping was carried out by means of a validated high performance liquid chromatography assay at baseline and under treatment. RESULTS: The distribution of GSTT1 genotypes was as follows: 31% *A/*A; 49% *A/*0; 20% *0/*0. GSTT1 phenotypes as expressed in enzyme activity significantly differed between conjugators classes. (P < 0.001). GSTT1 activity under treatment was significantly (P = 0.0001) increased when compared with baseline. There were no significant associations between the aforementioned GSTT1 pheno- and genotypes and clinical parameters such as psoriasis area and severity index (PASI)50, adverse effects and FAE dosage (P > 0.05), except for the frequent occurrence of reduction (>50%) of circulating lymphocytes in patients with *0/*0 GSTT1 status (P = 0.036; odds ratio: 6, 95% CI: 1.1-32). CONCLUSION: GSTT1 geno- and phenotypes significantly correlate in psoriasis patients and do not substantially differ from healthy controls. Response to FAE does likely not depend on GSTT1. However, *0/*0 GSTT1 status is a predictor for the occurrence of marked reduction of lymphocyte counts under FAE therapy. Notably, FAE seem to enhance GSTT1 enzyme activity in high and low conjugators.

Differential expression of connective tissue growth factor and extracellular matrix proteins in lichen sclerosus.

BACKGROUND: The histopathology of lichen sclerosus (LS) suggests abnormalities in extracellular matrix (ECM) composition. OBJECTIVES: We aimed to investigate the expression pattern of ECM proteins and related growths factors and Smad signal transducers in LS as compared with healthy skin. METHODS: To assess the expression of decorin, biglycan, versican, perlecan, fibronectin, dermatopontin, extracellular matrix protein 1 (ECM-1), matrix metalloproteinase 1, tissue inhibitor of metalloproteinase 1, connective tissue growth factor (CTGF), transforming growth factor ß1, and Smad-3 protein, real-time RT-PCR and immunohistochemistry were performed on skin specimens obtained from the genital region of healthy subjects (n = 10) as well as LS patients (n = 26). RESULTS: Median mRNA as well as mean protein expression of biglycan, versican, fibronectin, and ECM-1 was significantly higher in LS when compared with healthy controls. Both mRNA and protein CTGF expression observed in LS was significantly higher than in controls. CTGF mRNA expression significantly correlated with mRNA expression of biglycan, versican and fibronectin. CONCLUSIONS: Expression of ECM proteins (e.g. proteoglycans, ECM-1) and CTGF is altered in LS. TGF-ß/Smad-3 independent up-regulation of CTGF may induce accumulation of ECM proteins and maintain fibrosis in chronic LS.

Etanercept plus narrowband ultraviolet B phototherapy of psoriasis is more effective than etanercept monotherapy at 6 weeks.

BACKGROUND: A substantial portion of patients with psoriasis does not achieve a satisfactory response under antitumour necrosis factor (TNF)-α biological therapies. OBJECTIVES: We aimed to evaluate whether etanercept plus narrowband ultraviolet B (NB-UVB) phototherapy is superior to etanercept monotherapy in the management of psoriasis. METHODS: In this prospective study, patients with psoriasis were treated with etanercept 25 mg twice weekly. Two marker lesions were selected for determination of the modified Psoriasis Area and Severity Index (M-PASI). NB-UVB was administered thrice weekly whereby one marker lesion was covered as nonirradiated control. Skin biopsies for histology and immunohistochemistry were performed in both marker lesions after a 6-week treatment course. RESULTS: After 6 weeks of therapy, the relative M-PASI reduction (mean ± SD) in etanercept-treated sites (53·7 ± 36·9%) was significantly lower than the reduction in etanercept plus NB-UVB-treated lesions (64 ± 27·8%; P = 0·011). At the end of treatment, histology scores of etanercept-treated psoriatic plaques were significantly higher than scores of etanercept plus NB-UVB-treated sites (4·6 ± 2·7 vs. 3·7 ± 2·4; P =0·045). Epidermal immunoreactivity for CD1a, CD4 and CD8 was significantly lower in etanercept plus NB-UVB-treated lesions when compared with etanercept monotherapy. CONCLUSIONS: Etanercept combined with NB-UVB is more effective than etanercept monotherapy at 6 weeks as demonstrated at a clinical, histological and immunohistological level. However, as there is an increased risk for malignancy by treatment with TNF-α blockers alone or in combination with phototherapy, we recommend to restrict this highly effective combination to short periods of time, for instance to obtain a quicker response, and to avoid long-term treatment.

Expression of antimicrobial peptides and proteins in etanercept-treated psoriasis patients.

Recent papers highlight the role of dysregulated expression of antimicrobial peptides and proteins (AMPs) in the pathogenesis of psoriasis. Etanercept, a blocker of the pro-inflammatory cytokine tumour necrosis factor-α (TNF-α), is effective in the treatment of psoriasis. We aimed to evaluate the expression profiles of AMPs in psoriatic skin before and after a 6-week course of etanercept therapy. We included 12 psoriasis patients who underwent medium-dose etanercept treatment for 6weeks. At baseline and at the end of therapy immunohistochemistry from lesional skin was performed for psoriasin, LL-37, and human ß-defensin 2 (hBD-2). After 6-week treatment, the modified psoriasis area and severity index significantly decreased from 37.5±5.9 to 14±13.4. Lesional immunoreactivity scores of psoriasin, LL-37, and hBD-2 also significantly decreased after a 6-week course of etanercept. We have demonstrated that etanercept-induced improvement of psoriasic lesions is associated with a significant decline of AMP protein expression.

Impact of etanercept treatment on ultraviolet B-induced inflammation, cell cycle regulation and DNA damage.

BACKGROUND: Current studies indicate that treatment with tumour necrosis factor (TNF)-α blockers plus ultraviolet (UV) B phototherapy results in higher relative Psoriasis Area and Severity Index reduction as compared with TNF-α monotherapy. OBJECTIVES: This study aimed to investigate the acute impact of etanercept on UVB-induced inflammation, cell cycle regulation and DNA damage. METHODS: Eleven subjects diagnosed with psoriasis who fulfilled the indication criteria for etanercept treatment were studied. A healthy skin site on the upper back was treated with UVB at 2 minimal erythema doses (MED). After 1, 24 and 72 h punch biopsies were taken from this site. Following the 72 h biopsy etanercept 50 mg was administered subcutaneously. After 48 h, 2 MED was given on healthy skin adjacent to previously treated skin sites. Again, after 1, 24 and 72 h punch biopsies were taken from this site. UVB- as well as UVB plus etanercept-treated skin was assessed by means of colorimetry and immunohistochemical studies for caspase 3, cyclin D(1), interleukin-12, Ki-67, p16, p53, survivin, thymine dimers and TNF-α. RESULTS: Erythema formation did not differ significantly between UVB- and UVB plus etanercept-treated sites. Comparisons between UVB- and UVB plus etanercept-treated sites at a given time (1, 24, 72 h) did not result in significant differences in immunoreactivity of the markers investigated, except for cyclin D(1), p53 and survivin. Immunoreactivity of cyclin D(1) and p53 was significantly decreased in UVB plus etanercept-treated sites at 24 h. Survivin expression was significantly higher in UVB plus etanercept-treated skin as compared with UVB monotherapy. CONCLUSIONS: Our data indicate that combined treatment with broadband UVB and TNF-α blockers might increase the risk of photocarcinogenesis by influencing apoptotic as well as antiapoptotic pathways.

Absolute count of T and B lymphocyte subsets is decreased in systemic sclerosis.

BACKGROUND: Previous reports on lymphocyte subpopulations in systemic sclerosis (SSc) are conflicting. Therefore, we aimed to investigate the lymphocyte subsets in SSc patients who were not on immunosuppressive therapy. METHODS: Lymphocyte subsets were assessed in the peripheral blood of SSc patients (n = 29) and healthy controls (n = 29) using the four colour flow cytometry method. Correlation studies were also performed in order to assess the relationship between lymphocyte subsets and clinical parameters. RESULTS: The absolute count of lymphocytes (P = 0.0042), CD3+ (P = 0.0014), CD4+ (P = 0.0070), CD8+ (P = 0.021), and CD19+ cells (P = 0.024) was significantly decreased in SSc patients when compared to healthy controls. CD4+/CD8+ ratio and the absolute count of CD56+ cells observed in SSc patients did not significantly differ from controls (P=0.165; P = 0.632, respectively). There was no substantial relationship between the lymphocyte subset levels and clinical features (i.e., SSc subtype, autoantibody profiles, organ involvement), except for a significant inverse correlation of CD19+ cells and the modified Rodnan skin score (r = -0.43, P = 0.020). CONCLUSION: Our data support previous reports indicating that subsets of T lymphocytes as well as B lymphocytes play a role in the pathogenesis of SSc.

Clonal T-cell populations are frequent in the skin and blood of patients with systemic sclerosis.

BACKGROUND: Pilot studies were suggestive for a role of clonal T cells in the pathogenesis of systemic sclerosis (SSc). OBJECTIVES: To investigate the presence of clonal T cells in both peripheral blood and skin of a large collection of patients with SSc. METHODS: Polymerase chain reaction and high-resolution capillary electrophoresis for detecting T-cell clonality were performed in a series of 126 patients with SSc. RESULTS: Seventy-seven (61%) of 126 patients had clonal T cells in their peripheral blood. In contrast, a clonal T-cell population was present in only four of 29 (14%) age-matched healthy controls (P = 0.03). Older patients were more likely to have clonal T cells than younger patients with SSc (P < 0.0001). Clonal T cells were more commonly detected in the blood of patients with limited cutaneous SSc (48 of 65 patients, 74%) than in those with diffuse cutaneous disease (29 of 61, 48%; P = 0.0002). Lesional skin specimens from 20 of 44 patients (45%) had detectable clonal T-cell populations. There was no correlation between the presence of circulating clonal T cells and lesional clonal T cells, sex, disease duration, extent of skin sclerosis, digital ulcers, organ involvement (e.g. interstitial lung disease, kidney disease, oesophagus involvement), treatment of SSc, or autoantibody profile. CONCLUSIONS: Many patients with SSc have expanded clonal T cells in their peripheral blood and skin. These clonal T cells could play a critical role in the pathogenesis of SSc, especially in limited cutaneous disease.

Significant upregulation of antimicrobial peptides and proteins in lichen sclerosus.

BACKGROUND: Lichen sclerosus (LS) is a chronic inflammatory T cell-driven sclerotic skin condition in which skin barrier disruption frequently occurs. Inflamed and injured epithelia are a particularly rich source of antimicrobial peptides and proteins (AMPs). OBJECTIVES: We aimed to investigate for the first time the expression pattern of AMPs in lesions of LS as compared with healthy skin. METHODS: Twenty-four women with LS as well as 10 healthy women were included in the study. In order to assess the expression of human beta-defensin (hBD)-1, hBD-2, hBD-3, psoriasin (S100A7), the cathelicidin LL-37 and RNase 7, real-time reverse transcriptase-polymerase chain reaction and immunohistochemistry were performed on skin specimens obtained from lesional and healthy skin of the genital region, respectively. RESULTS: Median hBD-2 mRNA levels observed in LS were significantly higher than in controls (0.15 vs. 0.008; P = 0.0037). Moreover, psoriasin (98.2 vs. 28.1; P = 0.0052) mRNA expression was significantly higher in LS lesions as compared with controls. Significant differences in mRNA expression of hBD-2 and psoriasin were also confirmed by immunohistochemistry. For hBD-1, hBD-3, LL-37 and RNase 7, levels did not differ significantly or were significant only at the gene level but not protein level. CONCLUSIONS: We have demonstrated that hBD-2 and psoriasin expression levels in lesional skin of patients with LS are significantly increased when compared with healthy controls. Whether this observation simply reflects an innate defence response caused by an increased risk of local infection, or whether our data indicate a pathogenetic role of AMPs in LS, will be addressed in future studies.

Magnetic-field-induced optical transmittance in colloidal suspensions.

Through simulation and experiment we demonstrate that when a magnetic field is applied to a suspension of magnetic particles, the optical attenuation length along the direction of the field increases dramatically, due to the formation of chainlike structures that allow the transmission of light between the strongly absorbing particles. This phenomenon is interesting for two reasons; first, there might be practical applications for this effect, such as optical-fiber-based magnetic field sensors, and second, measuring the time evolution of the optical attenuation length enables us to determine the kinetics of structure formation, which can be compared to the predictions of simulation and theory. In agreement with both simulation and theory, the optical attenuation length increases as a power of time, but much less light is actually transmitted than expected, especially at higher particle concentrations. We conclude that particle roughness, which is not included in either theory or simulation, plays a significant role in structural development, by pinning structures into local minima.