Wolfgang Salmhofer

A genome-wide association study identifies new psoriasis susceptibility loci and an interaction between HLA-C and ERAP1

To identify new susceptibility loci for psoriasis, we undertook a genome-wide association study of 594,224 SNPs in 2,622 individuals with psoriasis and 5,667 controls. We identified associations at eight previously unreported genomic loci. Seven loci harbored genes with recognized immune functions (IL28RA, REL, IFIH1, ERAP1, TRAF3IP2, NFKBIA and TYK2). These associations were replicated in 9,079 European samples (six loci with a combined P < 5 × 10−8 and two loci with a combined P < 5 × 10−7). We also report compelling evidence for an interaction between the HLA-C and ERAP1 loci (combined P = 6.95 × 10−6). ERAP1 plays an important role in MHC class I peptide processing. ERAP1 variants only influenced psoriasis susceptibility in individuals carrying the HLA-C risk allele. Our findings implicate pathways that integrate epidermal barrier dysfunction with innate and adaptive immune dysregulation in psoriasis pathogenesis.

Borderline pulmonary arterial pressure is associated with decreased exercise capacity in scleroderma.

RATIONALE Pulmonary arterial hypertension is associated with impaired exercise capacity and decreased survival in patients with scleroderma. Randomized controlled studies showed significant benefit of targeted therapies in patients with a resting mean pulmonary arterial pressure (MPAP) greater than 25 mm Hg. The clinical relevance of pulmonary arterial pressure values in the upper normal range is unknown. OBJECTIVES To examine the clinical relevance of pulmonary arterial pressure in scleroderma patients. METHODS After a noninvasive screening program, 29 patients with systemic sclerosis without significant lung fibrosis and without known pulmonary arterial hypertension underwent right heart catheterization and simultaneous cardiopulmonary exercise test. A six-minute walk distance (6MWD) was determined within 48 hours. MEASUREMENTS AND MAIN RESULTS A resting MPAP above the median (17 mm Hg) was associated with decreased 6MWD (396 +/- 71 vs. 488 +/- 76 m; P < 0.005) and peak Vo(2) (76 +/- 11% vs. 90 +/- 24%; P = 0.05). Resting pulmonary vascular resistance was inversely correlated with 6MWD (r = 0.45; P < 0.05). At 25 and 50W, MPAP above the median (23 and 28 mm Hg) was associated with decreased 6MWD (P < 0.005; P < 0.0005). At peak exercise, MPAP showed no association with 6MWD or peak Vo(2); however, cardiac index was positively (r = 0.45; P < 0.05) and pulmonary vascular resistance was negatively correlated with 6MWD (r = -0.38; P < 0.05). CONCLUSIONS MPAP and resistance in the upper normal range at rest and moderate exercise are associated with decreased exercise capacity and may indicate early pulmonary vasculopathy in patients with systemic sclerosis. Investigations on the prognostic and therapeutic implications of such borderline findings are warranted. Clinical trial registered with http://www.clinicaltrials.gov (NCT00609349).

Assessment of Pulmonary Arterial Pressure During Exercise in Collagen Vascular Disease : Echocardiography vs Right-Sided Heart Catheterization

BACKGROUND This study compared the results of exercise Doppler echocardiography (EDE) with right-sided heart catheterization (RHC) and evaluated the combination of EDE and cardiopulmonary exercise testing (CPET) as a screening method for early pulmonary vasculopathy in patients with connective tissue disease. METHODS Patients (N = 52) with connective tissue disease (predominantly systemic sclerosis) and without known pulmonary arterial hypertension underwent both EDE and CPET. If systolic pulmonary arterial pressure (SPAP) was > 40 mm Hg during exercise or peak oxygen uptake (Vo(2)) was < 75% predicted, RHC was suggested. RESULTS EDE showed an SPAP > 40 mm Hg during exercise in 26/52 patients. Additionally, CPET showed a peak Vo(2) < 75% predicted in 10/26 patients with SPAP <or= 40 mm Hg upon exercise. Accordingly, RHC was suggested to 36 patients. RHC was performed in 28 of these patients, revealing SPAP > 40 mm Hg in 25 patients (n = 1 at rest, n = 24 during exercise). SPAP values assessed by EDE showed no significant difference vs RHC at rest, 25 W, 50 W, and maximal exercise (difference [95% CI]: 0.3 [-2.7; 3.2], -1.3 [-7.1; 4.4], 0.9 [-7.7; 5.9], and -5.6 [-13.5; 2.2] mm Hg). Eight patients with exercise SPAP > 40 mm Hg had an exercise pulmonary arterial wedge pressure > 20 mm Hg, suggesting exercise-induced left ventricular diastolic dysfunction not detectable by EDE. CONCLUSIONS EDE appears to be a reasonable noninvasive method to detect SPAP increase during exercise in connective tissue disease. In combination with CPET, it may be a useful screening tool for early pulmonary vasculopathy, although RHC remains the gold standard for hemodynamic assessment. TRIAL REGISTRATION clinicaltrials.gov; Identifier: NCT00609349 (Early Recognition of Pulmonary Arterial Hypertension).

Feasibility and acceptance of telemedicine for wound care in patients with chronic leg ulcers

We examined the feasibility and acceptance of teledermatology for wound management of patients with chronic leg ulcers by home-care nurses. Forty-one chronic leg ulcers of different origin in 14 patients were included. After an initial in-person visit in which leg ulcers were assessed and classified, and underlying diseases noted, follow-up visits were done by home-care nurses. Once a week 1–4 digital images of the wound and surrounding skin and relevant clinical information were transmitted via a secure Website to an expert at the wound care centre. The experts provided an assessment of wound status and therapeutic recommendations. In 89% of the 492 teleconsultations, the quality of images was sufficient or excellent and the experts were confident giving therapeutic recommendations. Treatment modalities were changed or adapted in one-third of the consultations. There was a significant decrease in visits to a general physician or the wound care centre. The acceptance of teledermatology was high in patients, home-care nurses and wound experts. Teledermatology offers great potential for chronic wound care and seems to be accepted both by patients and health-care persons.

CLINICAL AND HISTOPATHOLOGIC SPECTRUM OF PILOMATRICOMAS IN ADULTS

Background. Pilomatricomas are benign cutaneous neoplasms with differentiation toward hair matrix. Although previously reported to occur mostly in children and young adults, Taaffe et al. recently observed a second onset peak in adults and the elderly.

Treatment with 311-nm ultraviolet B accelerates and improves the clearance of psoriatic lesions in patients treated with etanercept

Background  Some patients with plaque‐type psoriasis respond slowly to treatment with etanercept. In such cases combining etanercept with conventional treatments might be helpful.

Efficacy of psoralen plus ultraviolet A therapy vs. biologics in moderate to severe chronic plaque psoriasis: retrospective data analysis of a patient registry.

Background  Few studies have directly compared the clinical efficacy of psoralen plus ultraviolet A (PUVA) vs. biologics in the treatment of psoriasis.

Treatment with 311-nm ultraviolet B enhanced response of psoriatic lesions in ustekinumab-treated patients: a randomized intraindividual trial

Background  Treatment with the interleukin‐12/23 antibody ustekinumab produces a satisfactory response [i.e. 75% reduction in Psoriasis Area and Severity Index (PASI) compared with baseline (PASI 75)] in the majority of patients with moderate to severe chronic plaque‐type psoriasis.

Influence of skin tension and formalin fixation on sonographic measurement of tumor thickness

BACKGROUND High-resolution sonographic measurement of skin tumors, especially of malignant melanomas, allows presurgical assessment of the most important prognostic factor--tumor thickness. A good correlation between ultrasonographic and histopathologic thickness measurement has been reported. Procedures for preparing tissue for histopathologic examination, such as excision, fixation in formalin, dehydration in alcohol, and embedding in paraffin, may cause the tissue to retract and shrink and may therefore affect thickness measurement results. OBJECTIVE Our purpose was to evaluate the influence of skin preparation procedures on ultrasound measurement results and to compare tumor thickness values obtained sonographically versus those obtained histopathologically. METHODS Sixty-three epithelial (n = 37) and melanocytic (n = 26) tumors, benign as well as malignant, were measured by ultrasound before and immediately after excision and after overnight fixation. Sonographically and histopathologically determined tumor thicknesses were compared. RESULTS Loss of skin tension after excision led to an increase in measured tumor thickness because of spherical retraction of the specimen. Subsequent fixation, dehydration, and embedding reversed this effect, so that altogether, histopathologically assessed tumor thickness was only slightly lower than ultrasound-derived thickness before excision. This was true for melanocytic as well as epithelial lesions. CONCLUSION Loss of skin tension after excision and tissue preparation procedures seem to offset each other and lead to a good overall correlation between ultrasonographic and histopathologic measurements.

Pilot study on the acceptance of mobile teledermatology for the home monitoring of high-need patients with psoriasis

Background/Objectives:  The willingness to be educated is one of the highest desires among patients with psoriasis. Therefore, a collaborative model of management would appear to be essential in enhancing patient satisfaction in this challenging condition. The present study aimed at examining the applicability of a mobile teledermatology service in this regard and assessing the association between patient acceptance and perceived health‐related quality of life.