Nick Othlinghaus

Differential mRNA Expression of Antimicrobial Peptides and Proteins in Atopic Dermatitis as Compared to Psoriasis Vulgaris and Healthy Skin

Background: Patients with atopic dermatitis (AD) are prone to have skin infections. We aimed to investigate mRNA expression levels of various antimicrobial peptides and proteins (AMPs) in AD patients, and compare it with psoriasis vulgaris (PV) patients and healthy subjects. Methods: Skin biopsies were obtained from healthy subjects and patients with AD and PV. Quantitative real-time RT-PCR was used to determine the mRNA levels of human β-defensin (hBD)-1, hBD-2, hBD-3, LL-37, psoriasin, RNase 7, interferon-γ, and interleukin-10 (IL-10). Results: Except for LL-37, mRNA of hBDs, psoriasin, and RNase 7 was significantly higher expressed in AD (n = 42) and/or PV (n = 35) patients when compared to controls (n = 18). While PV lesions showed significantly higher mRNA hBD-2 levels than lesions of AD, the latter was associated with significantly higher mRNA levels of RNase 7 when compared to PV. A significant positive correlation of hBD expression was observed both in AD patients and PV patients. hBD mRNA levels of AD skin correlated with psoriasin and RNase 7 levels. hBD-1 mRNA expression correlated with AD activity and IL-10 mRNA expression. Conclusions: Most AMPs investigated in this study proved to be overexpressed in AD as well as PV when compared to controls. However, a statistically significant difference in AMP mRNA expression between AD and PV was only found for hBD-2 and RNase 7. A moderate-to-strong linear relationship between the mRNA expression of particular AMPs appears to exist in AD, and to a lesser extent in PV as well.

Medium-dose ultraviolet (UV) A1 vs. narrowband UVB phototherapy in atopic eczema: a randomized crossover study

Background  Ultraviolet (UV) A1 and narrowband (NB)‐UVB have been reported to be effective treatments for atopic eczema (AE).

Gene expression of cytokines in atopic eczema before and after ultraviolet A1 phototherapy

Background Atopic eczema (AE) is a common pruritic and chronically relapsing inflammatory skin disease in which cytokines seem to represent important factors in the pathogenesis.

Effects of a Long-Pulsed 800-nm Diode Laser on Axillary Hyperhidrosis: A Randomized Controlled Half-Side Comparison Study

Background Generally, axillary hyperhidrosis (AH) is treated with antiperspirant agents, botulinum toxin, or local surgery. The effect of laser treatment on sweat secretion in patients with AH has not been investigated. Objective To evaluate the effect of diode laser epilation on the sweat rate of patients with AH. Materials and Methods We performed a randomized half‐side controlled trial. Twenty‐one patients were treated with 5 cycles of an 800‐nm diode laser. Sweat rates were documented using gravimetry and a visual analogue scale. Histologic examination was performed in all patients before and after treatment. Results A significant reduction in sweat rate was observed on the laser‐treated (median 89 mg/min, range 42–208 mg/min vs 48 mg/min, range 17–119 mg/min; p < .001) and the untreated contralateral (median 78 mg/min, range 25–220 mg/min vs median 65 mg/min, range 24–399 mg/min; p = .04) sides, although no significant difference was found between the treated and untreated sides (p = .10). Conclusion Although we observed a significant decrease in sweat rate on laser‐treated sites, laser epilation was not able to reduce the sweat rate significantly more than on the untreated contralateral side. These results probably indicate a placebo effect rather than a direct therapeutic effect of laser epilation.

Up-regulation of transforming growth factor-β3 and extracellular matrix proteins in acquired reactive perforating collagenosis

BACKGROUND Acquired reactive perforating collagenosis (ARPC) is an uncommon itchy dermatosis of unknown etiology. OBJECTIVES We aimed to study clinical features of ARPC and to characterize the expression profiles of proteins which are involved in extracellular matrix remodeling and wound repair. METHODS Seventeen patients with ARPC were included in the study. Immunohistochemical analyses were performed for CD34, factor VIIIa, vascular endothelial growth factor, matrix metalloproteinase-1 (MMP-1), tissue inhibitor of metalloproteinase-1 (TIMP-1), transforming growth factor-beta3 (TGF-beta3), Smad-3, and Smad-7. RESULTS Twelve patients (70.6%) had diabetes mellitus with disease duration of 14.6 +/- 13.1 years (mean +/- standard deviation). In all patients, chronic kidney disease was evident; two patients were receiving hemodialysis. Preexisting scabies infection was observed in 7 patients (41.2%). CD34 staining was significantly stronger in vessels of perilesional than those of lesional skin (P = .024). TGF-beta3, MMP-1, and TIMP-1 immunoreactivity was significantly stronger in lesional skin as compared with perilesional skin (P = .016, P = .0065, and P = .035, respectively). Although Smad-3 and Smad-7 immunoreactivity did not significantly differ in lesional and perilesional skin, there was a significant correlation between the protein expression of TGF-beta3 and Smad-3 (r = 0.56; P = .02), Smad-7 (r = 0.64; P = .006), and TIMP-1 (r = 0.56; P = .018) expression. LIMITATIONS We did not perform polymerase chain reaction studies on mRNA expression. CONCLUSIONS Our clinical data indicate that ARPC is etiopathogenetically linked to chronic kidney disease. Overexpression of TGF-beta3 and extracellular matrix proteins may represent antecedent tissue repair and therefore may be considered a significant event in the resolution of ARPC lesions.

A randomized, half-side comparative study of aminolaevulinate photodynamic therapy vs. CO2 laser ablation in immunocompetent patients with multiple actinic keratoses

Background  Photodynamic therapy (PDT) and laser ablation (LA) are frequently used treatment options for multiple actinic keratoses (AK), yet they have not been compared head to head.

Clinical Characteristics and Survival Data of Melanoma Patients With Nevus Cell Aggregates Within Sentinel Lymph Nodes

Histopathologic differentiation of nevus cell aggregates and metastatic melanoma in lymph nodes is challenging. Patients with melanoma who had undergone sentinel lymph node (SLN) biopsy were evaluated using univariate and multivariate analyses as well as Kaplan-Meier statistics. Of the 651 patients, 50 (7.7%) had a nodal nevus in the SLN. In the logistic regression model, primary melanoma on the lower extremities proved to be the strongest independent negative predictor of nodal nevi with an odds ratio of 0.11 (95% confidence interval, 0.034-0.36; P = .0002). Overall 5-year survival (P = .17) and 5-year disease-free survival (P = .45) of patients with nodal nevi did not significantly differ from that of patients with negative SLNs. The frequency and anatomic localization of nodal nevi observed in the present study are in line with previous studies. Our 5-year survival data clearly demonstrate that nevus cell aggregates in lymph nodes have to be considered a benign condition even though it occurs in patients with melanoma. This study provides an indirect proof of validity and accuracy of current histopathologic methods for differentiation between nodal nevi and melanoma metastasis.

Tacrolimus ointment neither blocks ultraviolet B nor affects expression of thymine dimers and p53 in human skin

BACKGROUND There is a lack of data with regard to the interaction between ultraviolet (UV) radiation and topical calcineurin inhibitors. OBJECTIVE We aimed to investigate (1) the UV transmission through tacrolimus ointment and (2) the impact of topical exposure to tacrolimus on the protein expression of thymine dimers (TD) and p53 in human skin. METHODS Spectrophotometric measurements (290-400 nm) of tacrolimus ointment and the vehicle were performed. Eight subjects were treated with tacrolimus ointment and the vehicle thrice daily over a 3-day period on the back. Pre-treated sites and one control site were exposed to two minimal erythema doses UVB. Skin biopsies were taken 1h and 24h after irradiation. Immunohistochemical procedures were used for the detection of TD and p53. RESULTS Mean UV transmission was over 94% and did not significantly differ between tacrolimus ointment and the vehicle. Immunohistological examinations of TD and p53 expression did not demonstrate significant differences between irradiated sites, irradiated plus vehicle treated sites, and irradiated plus tacrolimus treated sites both 1h and 24h post-irradiation. CONCLUSIONS The present data suggest that tacrolimus ointment hardly has UV blocking capacities and does not significantly interfere with development and/or removal of local DNA damage in human skin.

Interstitial Granulomatous Dermatitis Associated with Myelodysplastic Syndrome - Complete Clearance under Therapy with 5-azacytidine

Granulomatous skin diseases comprise a heterogenous spectrum of dermatoses that are characterised by a dermal infiltrate of predominantly histiocytes (1). Among this group, interstitial granulomatous dermatitis (IGD) is a term introduced by Ackerman in 1993 (2). It describes a rare form of granulomatous, non-infectious, reactive dermatosis that is frequently associated with rheumatoid arthritis (3, 4). However, several reports of drug-induced IGD and IGD associated with haematological malignan-cies exist as well (5–8). We report a case of IGD with un-derlying myelodysplastic syndrome (MDS). Successful treatment of MDS with 5-azacytidine led to a complete clearance of IGD, which might indicate a pathogenetic relationship of both diseases in this patient. To our know-ledge, only one previous report exists on the coincidence of IGD and MDS (9). Our report further suggests to screen for MDS or other haematologic malignancies in patients with IGD.CASE REPORT

Impetiginized Wells’ syndrome in a patient with chronic lymphocytic leukaemia

Wells syndrome, also known as eosinophilic cellulitis, is a distinctive dermatosis with a wide range of morphological features ranging from acute cellulitis and urticaria-like lesions to bullous eruptions. Its aetiology and pathogenesis are unknown, but the disease has been found to be associated with malignancies, and recurrences can often be related to infections, arthropod bites, drug administration or surgery. A 78-year-old man presented with a 3-year history of recurrent erythematous, slightly indurated nodules and plaques with yellowish crusts mainly affecting the face and neck (Fig. 1). He had been diagnosed in 2001 as having Rai stage IV classic B-cell chronic lymphocytic leukaemia (CLL), and was admitted to our inpatient clinic in September 2006. He had undergone several cycles of chemotherapy including fludarabine (2002, 2003) and bendamustin (March 2006). After each treatment, he attained partial remission followed by moderate tumour regrowth (splenomegaly, lymphocytosis and ⁄ or anaemia). Biopsy specimens were taken from three different sites on the face, and histological examination found dense eosinophilic infiltrates within the entire dermis and parts of the subcutis (Fig. 2). Immunohistochemistry did not show any increased immunoreactivity for CD19, CD20 or Ki67. Thus, specific lymphocytic infiltrates of CLL could broadly be excluded. Periodic-acid–Schiff staining was negative for fungal agents. Swabs from the lesions on the forehead produced a heavy growth of methicillin-resistant Staphylococcus aureus, which was sensitive to doxycycline. Lymph node and abdominal ultrasonography, and computed tomography of the thorax and abdomen, did not show pathologies, except for splenomegaly