Severin Läuchli

Nephrogenic fibrosing dermopathy treated with extracorporeal photopheresis

Nephrogenic fibrosing dermopathy (NFD) is a rare fibrosing skin disease of unknown etiology occurring in patients with terminal renal disease. It was first described in the year 2000. The histology of NFD shows an increased number of dendritic cells, fibroblasts and thickened collagen fibers resembling scleromyxedema. It can be distinguished from scleromyxedema by a different distribution pattern of the skin lesions with indurated plaques mainly on the extremities and the absence of paraproteinemia. As yet, no treatment for NFD has been proven to be uniformly efficient. We describe the case of a 40-year old patient with renal insufficiency who was treated with hemodialysis and who had undergone kidney transplantation. Two years after transplantation, she developed sclerodermiform brownish plaques on her extremities. The induration improved significantly after 4 cycles of extracorporeal photopheresis.

Squamous cell carcinoma of the skin shows a distinct microRNA profile modulated by UV radiation.

investigated CHR expression in mast cells just in vicinity of eccrine glands. Serial sections were alternatively stained with toluidine blue and with anti-CHRM3 antibody. Mast cells were identified by positive toluidine blue staining (Figure 2c, upper panel), and CHRM3 expression by mast cells was examined in the antibody-stained adjacent sections (Figure 2c, lower panel). In a normal control, mast cells expressed CHRM3 at high levels. Mast cells in conjunction with the secretory portion expressed CHRM3 in the hypohidrotic but not anhidrotic areas. There was no significant difference in the number of mast cells between the anhidrotic and hypohidrotic areas. Our study revealed that the skin of patients with CUAH is divided into the wheal-non-occuring anhidrotic and wheal-occuring hypohidrotic areas. Even in the hypohidrotic areas, the intradermal injection of autologous sweat did not yield wheal, suggesting the absence of sweat allergy (Tsuchiya et al., 2004). We found the lack of CHRM3 expression in the anhidrotic skin, which may lead to the lack of sensitivity to acetylcholine. Mast cells are responsible for wheal formation and present just in the vicinity of eccrine glands. Neither eccrine gland cells nor mast cells expressed CHRM3 in the anhidrotic area, and it is thus reasonable that sweating and wheal formation were absent in this area. CHR mediates wheal development (Tong et al., 1997), and acetylcholine can induce degranulation of mast cells (Fantozzi et al., 1978; Blandina et al., 1980). In the hypohidrotic area, we are tempting to speculate that acetylcholine released from nerves upon exercise cannot be completely trapped by CHR of eccrine glands and overflows to the adjacent mast cells. In this scenario, mast cells may be capable of producing histamine and resultant wheal in response to acetylcholine because of the expression of some degree of CHRM3.

Diagnostic delay in hidradenitis suppurativa is a global problem.

DEAR EDITOR, Hidradenitis suppurativa (HS) is clinically defined with recognized diagnostic criteria and recognizable physical characteristics. Untreated, the disease causes significant morbidity. The prevalence varies between 0 0003% and 4% depending on the study population. Estimates from insurance databases suggest a prevalence of < 0 1%. This variation strongly suggests a significant selection bias or misclassification, and it may be speculated that not all patients present for care. This is reinforced by clinical experience and published evidence indicating a significant delay in diagnosis. This study explores the delay in diagnosis for patients with HS on an international level. The study (survey) was conducted in 2013. Observational data were collected during routine visits or extracted from case records. Because of the simple and obvious symptomatology of recurrent painful lesions present in restricted welldefined areas of the body, patients’ self-reported history was considered valid regarding onset of symptoms. Consecutive patients with HS and psoriasis were included from each participating centre during a period of 4 months or less. The data were anonymized by removing any names, addresses and social security numbers, and included age, sex, age at disease onset, age at diagnosis, delay in diagnosis, time from onset of symptoms to first physician contact, age at first medical contact, number of physicians seen prior to the diagnosis, family history and disease severity. If the diagnosis was made by a primary care physician or by a specialist other than a dermatologist prior to seeing a dermatologist, this was recorded as the date of the diagnosis. Individual centres were responsible for and obtained any locally required permissions and signed informed consent forms, for example ethics committee approval, in accordance with national registry and data protection rules. Patients diagnosed with HS or psoriasis (and confirmed by the investigator) were included. The primary outcome was quantification of the delay in diagnosis. Additionally, documentation was made of both the delay in visiting a physician (and so gaining access to specialist treatment) and the relative delay in diagnosis of HS compared with psoriasis with/without a family history. The severity of HS was determined by Hurley’s staging criteria: stage I, mild; stage II, moderate and stage III, severe. In patients with psoriasis, severity was evaluated by the Psoriasis Area and Severity Index: score < 7, mild; 7–12, moderate and > 12, severe. The t-test, Wilcoxon rank sum test and v-test were used where appropriate. Univariate and multivariate logistic regression analyses were used to identify factors predictive of significant diagnostic delay. Diagnostic delay > 2 years was defined as significant. Diagnosis, sex, age of onset, family history and disease severity were selected as potentially important

Martorell Hypertensive Ischemic Leg Ulcer A Model of Ischemic Subcutaneous Arteriolosclerosis

OBJECTIVES To better define the diagnosis and treatment of Martorell hypertensive ischemic leg ulcer (HYTILU) and to compare Martorell HYTILU with calciphylaxis (calcific uremic arteriolopathy) and nonuremic forms of calciphylaxis. DESIGN Retrospective study from 1999 through 2007. SETTING Department of Dermatology, University Hospital of Zurich, Zurich, Switzerland. PARTICIPANTS Of 330 patients with leg ulcers, 31 had a clinical diagnosis of Martorell HYTILU confirmed by dermatopathologic examination. MAIN OUTCOME MEASURES Clinical features, suspected diagnosis at initial presentation, cardiovascular risk factors, findings from vascular examination and histologic analysis, specific medical and surgical management, and outcome. RESULTS Of the 31 patients, all presented with 1 or multiple painful necrotic skin ulcers on the laterodorsal part of the leg, with bilateral involvement in 16 of 31 cases (52%), and 16 were referred with suspected pyoderma gangrenosum. All patients had arterial hypertension, and 18 (58%) had diabetes. All patients had subcutaneous stenotic arteriolosclerosis on histologic analysis, with medial calcification in 22 of 31 of cases (71%). Martorell HYTILU, calciphylaxis, and nonuremic forms of calciphylaxis shared identical histologic features. Of the 31 patients, 29 (94%) were successfully treated with surgical debridement and split-thickness skin grafting. Three patients (9%) died of sepsis, 2 of whom were undergoing immunosuppressive treatment for wrongly diagnosed pyoderma gangrenosum. CONCLUSIONS Ischemic subcutaneous arteriolosclerosis is the hallmark of Martorell HYTILU, calciphylaxis, and the nonuremic forms of calciphylaxis. All patients are hypertensive and approximately 60% are diabetic. Martorell HYTILU can easily be confused with pyoderma gangrenosum, which can be detrimental, since the 2 diseases require a completely different treatment strategy.

Immunosuppression affects CD4+ mRNA expression and induces Th2 dominance in the microenvironment of cutaneous squamous cell carcinoma in organ transplant recipients.

Squamous cell carcinoma (SCC) is the most frequent cancer in organ transplant recipients (OTRs). The immune system plays a major role in the fight against SCC, however, little is known about the local inflammatory response in SCC at all. We analyzed quantity and quality of the perineoplastic inflammatory SCC microenvironment in immunocompetent patients and immmunosuppressed OTRs. RNA expression profile of SCC patients was analyzed for 8 different sets of genes relating to Th1 versus Th2 response using Gene Set Enrichment Analysis. SCC from immunocompetent patients and OTRs were analyzed by real-time polymerase chain reactions for CD4, CD8, TBET, GATA-3, FOXP3, RORC, IFN-γ, IL-4, TGF-&bgr;, IL-10, and IL-17A mRNA expression. Immunohistochemistry was carried out in SCC for CD3, CD4, CD8, and FOXP3 expression. Considerable inflammation was seen in both patient groups. SCC in immunocompetent patients and OTRs was associated with a mixed Th1 and Th2 gene expression signature. CD4+ mRNA was diminished in immunosuppression. Skin adjacent to SCC in OTRs showed Th2 expression pattern as compared with immunocompetent patients. T-BET and IFN-γ mRNA expression were decreased in the OTR group. Although Th17-weighted inflammation was unchanged, IL-17A mRNA level was markedly decreased with immunosuppression. Regulatory T cells, characterized by FOX-P3 and TGF-β mRNA level, were decreased in OTRs. Our findings support the hypothesis that nontumor-bearing skin adjacent to SCC in OTRs is not necessarily normal and that the local microenvironment may contribute to a field effect contributing to higher recurrence rates and more aggressive behavior observed in these patients.

Excimer Laser versus Narrow-Band UVB (311 nm) in the Treatment of Psoriasis Vulgaris

Background: The excimer laser is a new therapeutic option in the treatment of psoriasis vulgaris. Objective: The purpose of this study was to determine the response of psoriasis lesions to the 308-nm excimer laser compared to 311-nm UVB phototherapy. Methods: In this prospective right/left comparative, open, single-blinded trial, selected psoriasis plaques of 16 patients were treated with the excimer laser whereas the rest of the body was treated with UVB narrow-band phototherapy. A modified PASI score was used to evaluate the results. Results: After 12 treatments, 15 patients were evaluated. In 2 patients no difference between the two body sides was observed. In 9 patients the laser-treated lesions showed better results, whereas in 4 patients the side treated with 311-nm UVB showed more clearing. The mean reduction in PASI score was 5.6 and 4.9, respectively (difference not significant). Conclusion: The use of the 308-nm xenon chloride excimer laser is an additional effective therapeutic option for the treatment of psoriasis vulgaris.

EpiDex® Swiss field trial 2004-2008.

Background: Approximately 20% of leg ulcers remain unresponsive to the best conservative standard of care. So far, these patients could either receive conventional skin grafts or had to accept their intractable wound. Skin substitutes from cell culture may represent a promising alternative to heal a major part of these patients on a non-surgical, potentially more cost-effective basis. Objective: To systematically evaluate the first 68 patients treated in Switzerland (Swiss EpiDex® field trial 2004–2008). Methods: Retrospective study on EpiDex treatment of a complete consecutive series of 68 patients with chronic wounds (66 chronic leg ulcers, 2 sores) unresponsive to best conservative standard of care. The primary end point was complete wound closure within 9 months after transplantation, the secondary end points change of wound surface area, pain reduction and overall judgement by the patient. Adverse effects were infection, dermatitis and others. Calculation of treatment costs was made. Results: By the end of the study, 50/68 (74%) of patients had their wound completely healed [venous 29/37 (78%); mixed 7/9 (78%); others 14/22 (64%)]; 10/68 (15%) had the wound surface area reduced by >50%, and 8/68 (12%) did not respond to the EpiDex treatment. Wound pain disappeared completely in 78% and partially in 13%. Fifteen patients (22%) received antibiotics for wound infection, and 2 (3%) developed dermatitis (not related to the local therapy). Average treatment costs for venous ulcers amounted to EUR 5,357, compared to EUR 5,722–8,622 reimbursed according to the German DRG system (2010) for an in-patient skin graft. Conclusion: EpiDex may effectively heal up to three quarters of recalcitrant chronic leg ulcers. Thus, it represents an intermediate step to avoid costly in-patient split-skin mesh graft treatments. Patients remain mobilized, and a donor site is avoided. Large wound size or a necrotic wound bed limit the use of EpiDex. Otherwise, it offers the opportunity to avoid conventional skin grafts in a significant number of chronic leg ulcer patients.

Safer sex behavior and alcohol consumption

To test the hypothesis that safer sex procedures are less consistently observed by persons under the influence of alcohol, data from the Swiss human immunodeficiency virus (HIV) Prevention Study (HIPS) were evaluated. HIPS is a large prospective cohort study involving 724 HIV-negative and mainly heterosexual subjects who entertain casual sexual contacts. Of the 724 participants, 36% reported that they had had sex while under the influence of alcohol. Of this group, 31% indicated that safer sex procedures were neglected owing to the influence of alcohol. No significant differences with regard to unprotected sexual intercourse were found between subjects who combine sex and alcohol and those who do not. The same was found to be true among subjects with different levels of general alcohol consumption. However, a significant correlation was found between the intensity of alcohol consumption (i.e., the quantity of alcohol intake per sitting) and the incidence of unprotected sexual intercourse. These findings show that the relationship between alcohol consumption and safer sex is complex; they also emphasize the need for preventive efforts to reinforce safer sexual behavior, for example through individual counseling of persons at risk for HIV-infection.

Kompressionstherapie bei Patienten mit Ulcus cruris venosum

Wund‐D.A.CH. ist der Dachverband deutschsprachiger Fachgesellschaften, die sich mit den Thematiken der Wundbehandlung beschäftigen. Experten verschiedener Fachgesellschaften aus Deutschland, Österreich und der Schweiz haben nun einen aktuellen Konsens der Kompressionstherapie für Patienten mit Ulcus cruris venosum erstellt.

Management of Split-Thickness Skin Graft Donor Sites: A Randomized Controlled Trial of Calcium Alginate versus Polyurethane Film Dressing

Background: Split-thickness skin graft (STSG) donor sites sometimes cause more postoperative morbidity for patients than the wound covered with the graft. Yet, there is no consensus on which dressings are best suited to treat these donor sites. Objective: To evaluate two commonly used modern wound dressings in the postoperative healing of STSG donor sites in a prospective randomized controlled trial. Methods: 38 patients were randomly assigned to treatment of an STSG donor site with an alginate dressing or a polyurethane film dressing. The primary outcome measures were postoperative pain scores, secondary outcome variables were time to epithelialization, dressing changes and complications. Results: Postoperative pain on day 1 was significantly lower in the polyurethane film group (2.05 vs. 0.79, p = 0.035) as compared to the alginate group. This difference was not detected on day 5 (0.89 vs. 0.53, p = 0.52). Time to epithelialization did not differ significantly between the two dressing groups. There were more dressing changes in the polyurethane film group and problems with leakage. Conclusion: Whereas film dressings resulted in initially lower pain scores, alginate dressings caused fewer additional dressing changes and less leakage.