Deep vein thrombosis after sclerotherapy and endovenous laser ablation of varicose veins - an observational study.

Background: The risk of developing deep vein thrombosis (DVT) after endovenous ablation of varicose veins varies in the literature. Little is known about the characteristics of this complication and associated factors. This study aimed: 1) to study the occurrence of DVT after ultrasound-guided foam sclerotherapy (UGFS) alone or combined with endovenous laser ablation (EVLA) for lower-limb varicose veins; 2) to identify factors associated with DVT. Patients and methods: The study included all outpatients aged 18 years or older who underwent UGFS and EVLA or UGFS alone at the University Hospital of Zurich between 2011 and 2015. Data were extracted from the hospital electronic medical record. Patients were surveyed about their level of pain after the procedure and their level of satisfaction with the procedure. Duplex ultrasound was used to assess the deep venous system 7-10 days and 6-8 months after the procedure. Regression analysis was used to examine the association of patient and procedure characteristics with the development of DVT. Results: A total of 334 patients (561 procedures performed in 393 different sessions) were included: 73% of the patients underwent combined UGFS and EVLA and 27% underwent UGFS alone. DVT occurred in 24 (7.2%) patients, of whom 88% underwent combined procedures and 17% underwent interventions involving both the great and small saphenous veins on the same session. DVT occurred in 8.2% of patients receiving thromboprophylaxis and in 9.5% of patients not receiving thromboprophylaxis. DVT occurred in 5.2% of women and 11.9% of men. No factors associated with a diagnosis of DVT after intervention were identified. Pain and satisfaction levels did not differ between patients with and without DVT. Conclusions: This study adds to the knowledge of the risk of DVT following UGFS alone or combined with EVLA. Further studies are needed to revise thromboprophylaxis.

Mediators of Capillary-to-Venule Conversion in the Chronic Inflammatory Skin Disease Psoriasis.

Psoriasis is a chronic inflammatory skin disease characterized by epidermal hyperplasia and hyperkeratosis, immune cell infiltration and vascular remodeling. Despite the emerging recognition of vascular normalization as a potential strategy for managing psoriasis, an in-depth delineation of the remodeled dermal vasculature has been missing. In this study, we exploited 5' single-cell RNA sequencing to investigate the transcriptomic alterations in different subpopulations of blood vascular and lymphatic endothelial cells directly isolated from psoriatic and healthy human skin. Individual subtypes of endothelial cells underwent specific molecular repatterning associated with cell adhesion and extracellular matrix organization. Blood capillaries, in particular, showed upregulation of the melanoma cell adhesion molecule as well as its binding partners and adopted postcapillary venule‒like characteristics during chronic inflammation that are more permissive to leukocyte transmigration. We also identified psoriasis-specific interactions between cis-regulatory enhancers and promoters for each endothelial cell subtype, revealing the dysregulated gene regulatory networks in psoriasis. Together, our results provide more insights into the specific transcriptional responses and epigenetic signatures of endothelial cells lining different vessel compartments in chronic skin inflammation.

Radiotherapy as a Treatment Option for Local Disease Control in Primary Cutaneous Diffuse Large B-Cell Lymphoma, Leg Type.

BACKGROUND: Primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL, LT) is an aggressive lymphoma variant. Anthracycline-based chemotherapy with rituximab is recommended as first-line treatment. Radiotherapy (RT) has been considered as a therapeutic option for local disease control in patients with solitary or localized lesions. METHODS: We report the results of a retrospective analysis of PCDLBC, LT patients treated either with RT alone or with physician's decision as first-line treatment, aiming to assess disease progression and/or first recurrence in these treatment groups. RESULTS: We retrospectively analyzed 20 patients treated either with RT alone (n = 8) or with investigator's choice treatment (n = 12), which included chemotherapy alone or combined with local therapy (RT and wide local excision). Complete response (CR) was achieved in 8 patients from the first group and 9 patients from the second group, with 1 treatment failure. Six patients treated with RT alone progressed with a median time to progression (TTP) of 12.5 months. In the second group, 5 patients progressed with a median TTP of 5.2 months. RT showed good local disease control in both groups without any skin relapses during the follow-up period. CONCLUSION: RT as first-line monotherapy followed by watchful waiting did not significantly improve the overall risk of disease progression but resulted in good local disease control. After progression, RT could still easily be combined with systemic treatment. The strength of this analysis needs to be evaluated in a larger patient cohort.

Compression Stocking With 100% Donning and Doffing Success: An Open Label Randomised Controlled Trial.

OBJECTIVE: The aim of this study was to test whether an investigational two layer stocking exerting 27-29 mmHg pressure at the medial supramalleolar level, but without compression in the foot and heel, is easier to put on and take off than a standard stocking of the same compression class (23-32 mmHg), and also to assess the prevention of diurnal oedema with both types of stocking. METHODS: This was an open label randomised controlled trial, which included 47 patients. All participants were at least 65 years of age and suffered from chronic venous disease class C3 - C6 in one leg. The primary end point was donning success; secondary endpoints were doffing success, prevention of diurnal oedema over one day, and the comfort of wearing the stocking. Patients were randomly allocated to one of two groups. Both types of compression stocking were compared in each group for ease of donning and doffing in the manner of a crossover study. Subsequently, patients wore the stocking type assigned to their group for a whole day to evaluate comfort and the effect on diurnal leg volume. RESULTS: All participants were able to don the investigational stocking unaided, compared with 75% for the standard stocking (p < .001). Unaided removal success was 100% with the investigational stocking vs. 66% for the standard stocking (p < .001). There was no significant difference in leg volume reduction between the study groups after a day of wear. The investigational stocking was also rated as being more comfortable than the standard stocking (p < .001). CONCLUSION: The investigational stocking, which has no compression in the foot or heel area, is significantly easier to don and doff, with no inferiority in oedema prevention, compared with a standard stocking of the same compression class.

Blockade of programmed cell death protein 1 (PD-1) in Sézary syndrome reduces Th2 phenotype of non-tumoral T lymphocytes but may enhance tumor proliferation.

Sézary syndrome (SS) is an aggressive leukemic variant of cutaneous T-cell lymphoma (L-CTCL) that arises from malignant clonally derived skin-homing CD4+ T cells. Based on advancements in our understanding of the mechanisms underlying L-CTCL, boosting the suppressed immune response emerges as a promising strategy in SS management. Immune checkpoint inhibitory molecules have already demonstrated efficacy in a wide spectrum of malignancies. Currently, agents targeting the programmed death-1 (PD-1) axis are under evaluation in L-CTCL. Here we investigated the expression of PD-1 and its ligands, PD-L1 and PD-L2 in blood and skin from patients with L-CTCL. We demonstrate that PD-1 expression is markedly increased on tumor T cells compared to non-tumor CD4+ T cells from SS patients and to CD4+ cells from healthy individuals. In contrast, PD-L1 shows decreased expression on tumor T cells, while PD-L2 expression is low without significant differences between these groups. Functional PD-1 blockade in vitro resulted in reduced Th2 phenotype of non-tumor T lymphocytes, but enhanced the proliferation of tumor T cells from SS patients. Our study sheds some light on the PD-1 axis in both peripheral blood and skin compartments in SS patients, which may be relevant for the treatment of L-CTCL with immune checkpoint inhibitor.

A Monocentric, Retrospective Analysis of 61 Patients with Generalized Granuloma Annulare.

BACKGROUND: Granuloma annulare is a chronic noninfectious granulomatous skin condition with variable clinical presentations. Generalized granuloma annulare, defined as widespread disease with >10 skin lesions, accounts for 15% of all cases. Numerous associated diseases have been controversially discussed, most importantly diabetes mellitus, dyslipidemia, thyroid disease, malignancy and systemic infections. OBJECTIVES: The objective of our study is to describe disease characteristics, treatment outcome and associated diseases in patients treated at the Department of Dermatology of the University Hospital Zurich during the last 20 years. METHODS: The hospital database was searched for patients with generalized granuloma annulare in the last 20 years (January 1, 1998, to December 31, 2017). Overall, 61 patients, 14 males and 47 females, were included in our study. The mean age was 58 years at first consultation. The diagnosis was verified clinically and histologically. RESULTS: Generalized granuloma annulare occurred at a mean age of 55 years, more commonly in females. Pruritus was absent in 51% of all patients. Metabolic diseases including diabetes mellitus, hypercholesterinemia and hypertriglyceridemia were present in 10.5, 8.2 and 4.9%, respectively. Thyroid disease was present in 9.8% and malignant disease in 23%, including colorectal cancer, lymphoproliferative disease, squamous cell carcinoma of the esophagus, basal cell carcinoma and gynecological malignancy. Therapy was initiated in 92%, while second- and third-line therapy was performed in 70 and 39%, respectively. Benefit during therapy (e.g., full and partial remission) was achieved in 39.3% during first-line, in 39.4% during second-line and in 33.8% during third-line treatment. Topical corticosteroids were the most commonly prescribed treatment, mostly leading to stable disease (46.6%). Combined full and partial remission occurred in a large proportion of patients receiving UVA1 (45%), PUVA (63.6%) and intralesional triamcinolone acetonide (100%). CONCLUSIONS: Generalized granuloma annulare is a mostly asymptomatic and benign disease with a strong tendency for treatment resistance. We suggest to screen all patients for dyslipidemia, thyroid disease and malignant disease. While randomized trials are needed, we suggest topical corticosteroids as the first-line treatment, intralesional triamcinolone acetonide for persistent solitary lesions and, if further treatment is needed, UVA1 or PUVA.

Sensitivity and specificity of T-cell receptor PCR BIOMED-2 clonality analysis for the diagnosis of cutaneous T-cell lymphoma.

BACKGROUND: Early and precise diagnosis of cutaneous T-cell lymphomas (CTCL) is challenging. Currently, polymerase chain reaction (PCR)-based clonality assessment of the T-cell receptor (TCR) is a helpful tool for this diagnosis. OBJECTIVES: In this retrospective study, we aimed to assess the sensitivity and specificity of this method for the diagnosis of CTCL. MATERIALS AND METHODS: Monoclonal rearrangement of the TCR was investigated retrospectively by PCR-based clonality assessment based on 292 DNA samples from skin biopsies of patients with a suspicion of CTCL. Algorithms were based on different ratios (three or five-fold difference) between the dominant PCR peak and the third highest PCR peak. RESULTS: A PCR peak five-fold higher than the third highest PCR peak demonstrated significantly greater specificity (83.7% versus 76.4%) but lower sensitivity (59.8% versus 68.6%) compared to a cut-off of three-fold higher. CONCLUSION: Our results confirm the diagnostic value of TCR clonality analysis which may be used to define the ideal cut-off in order to optimize sensitivity and specificity.

[Rosacea - manifestations and treatment options]. / Rosazea ­ Manifestationen und Therapiemöglichkeiten.

Rosacea - manifestations and treatment options Abstract. Rosacea is a common dermatosis of the face with a prevalence of up to 22 %, according to the current literature. The known trigger factors include caffeine, alcohol, sunlight, hot and spicy foods, psychological stress, menstruation and extreme temperatures or temperature fluctuations. Diagnosis is most often clinical, however, due to the numerous differential diagnoses, performing a biopsy may be helpful in atypical manifestations. Depending on the symptoms, in addition to the avoidance of trigger factors, physical therapeutic options as well as topical and systemic drugs are available.

Smoking does not Alter the Therapy Response to Systemic Anti-psoriatic Therapies: A Two-country, Multi-centre, Prospective, Non-interventional Study.

Psoriasis can involve the skin, joints, nails and cardiovascular system and result in a significant impairment in quality of life. Studies have shown a lower response rate to systemic anti-psoriatic therapies in smokers, and smoking is a trigger factor for psoriasis. The aim of this study was therefore to analyse the response to systemic therapies for psoriasis, with a focus on smoking. Prospectively collected data from patients with moderate to severe psoriasis included in the national psoriasis registries for Germany and Switzerland (PsoBest and SDNTT) were analysed. Therapy response was defined as reaching a Psoriasis Area and Severity Index (PASI) reduction of 75%, PASI ≤ 3 or Dermatology Life Quality Index (DLQI) ≤ 1. Out of 5,346 patients included in these registries, 1,264 met the inclusion criteria for this study. In the smoking group, 715 (60.6%) reached therapy response at month 3, compared with 358 (63.7%) in the non-smoking group (p ≤ 0.269), 659 (74.1%) vs. 330 (77%) reached therapy response at month 6 (p ≤ 0.097), and 504 (76.6%) vs. 272 (79.0%) at month 12 (p ≤ 0.611). Therefore, these data do not show that smoking affects the response rate of anti-psoriatic therapy after 3, 6 and 12 months.

Divergent LAG-3 versus BTLA, TIGIT, and FCRL3 expression in Sézary syndrome.

In Sézary syndrome (SS) impaired T-cell function and cytokine profile lead to immune evasion. Immune checkpoints non-redundantly regulate immune responses and targeting them is promising. We evaluated the expression of BTLA, CTLA-4, FCRL3, LAG-3, and TIGIT in tumor and non-tumor SS T-cells.Compared to CD4+ T helper cells from ten healthy individuals, tumor cells of eight SS patients had a significant upregulation of BTLA (1.5-fold; p < .0001), FRCL3 (2.2-fold; p < .0028) and TIGIT (2.2-fold; p < .0003) expression. In contrast, we found a reduced expression of LAG-3+ cells in the blood of tumor patients (0.5-fold; p < .0014). Only weak alternations between tumor, non-tumor cells, and healthy controls were observed regarding CTLA-4 (0.5-fold; p < .2022). Our results show a diverse expression pattern of immune-regulatory molecules in SS patients. As these molecules are essential in the regulation of T-cell mediated tumor surveillance and defense, their specific targeting might be of clinical relevance.

Potassium Iodide for Cutaneous Inflammatory Disorders: A Monocentric, Retrospective Study.

OBJECTIVES: Potassium iodide (KI) is a medication that has been used for decades in dermatology and it is mentioned as a treatment option in all major dermatology textbooks. Yet, there is little recent information on its efficacy. In our study, we wanted to retrospectively evaluate the therapy response to KI in our patients. METHODS: The hospital information system was searched for patients treated with KI at the Department of Dermatology (University Hospital Zurich) in the last 20 years (January 1, 1998 to December 31, 2017). A total of 52 patients were found and, subsequently, 35 patients were included in our study. RESULTS: KI was prescribed for the following skin conditions: erythema nodosum, disseminated granuloma anulare, necrobiosis lipoidica, nodular vasculitis, cutaneous sarcoidosis, and granulomatous perioral dermatitis/ rosacea. The median duration of KI intake was 5 ± 7.7 weeks (range 1-26). The global assessment of efficacy by the treating physician showed an improvement of disease in about a third of all patients. No response was seen in 14 patients and 9 even had a progression of disease. An adverse event was documented in 16 cases. CONCLUSIONS: Our findings show that an improvement was reached in only about a third of all cases. High response rates with only mild side effects (in 16 out of 35 patients) were observed.

TNFα and IL-17A are differentially expressed in psoriasis-like vs eczema-like drug reactions to TNFα antagonists.

BACKGROUND: Tumor necrosis factor α (TNFα) blocking drugs are in use for a wide range of autoimmune disorders. In up to 5% of patients, this class of drugs produces puzzling cutaneous side effects that are the subject of this investigation, namely psoriasiform and eczema-like skin inflammation. These side effects can occur after any time of treatment and regardless of the underlying disorders. The exact pathophysiology is as yet unknown. METHODS: A total of 33 patients (19 female, average age 52 years) who had a cutaneous reaction to infliximab, adalimumab or etanercept were included. The type of inflammatory reaction was determined, and the corresponding cytokine expression was evaluated by immunohistochemistry for TNFα, IL-1ß, IL-22, IL-6, IL-17A, IL33, IL-8 and IL-36α (semi-quantitative grading system from - to ++++). In addition, RNA expression levels of IL-17A and TNFα were confirmed by quantitative real-time PCR. RESULTS: IL-17A (P < .039) and TNFα (P < .008) were expressed at significantly higher levels in psoriasis or pustular-like reactions (PPR) compared to eczematous-like reactions (ELR). There was no significant difference in the expression of IL-1ß, IL-22, IL-6, IL-33, IL-8 and IL-36α between PPR and ELR. CONCLUSION: TNFα and IL-17A are both cytokines known to be involved in psoriasis but less so in non-psoriasiform dermatitis or eczema. Therefore, their overexpression in PPR is plausible and suggests that the pathogenesis of PPR mirrors at least in part those of psoriasis. Further investigations will define the exact role of these cytokines in rare cutaneous side effects of anti-TNFα therapy. Our results suggest that IL-17A inhibition could be a therapeutic option in patients with anti-TNF induced psoriasis.

[Leg ulcers (ulcus cruris): The frequent macrovascular causes]. / Ulcus cruris: Die häufigen, makrovaskulären Ursachen.

Leg ulcers (ulcus cruris): The frequent macrovascular causes Abstract. Four pathologies make up the macrovascular etiologies of leg uclers: Venous leg ulcers (50 %), mixed venous-arterial leg ulcers (20 %), arterial leg ulcers (5 %), and Martorell hypertensive ischemic leg ulcer (5 %). The remaining 20 % concern a large array of other etiologies. Every leg ulcer requires vascular (arterial and venous) work-up, that can be completed with microbiology, biopsy, and more in-depth internal diagnostics, as indicated. Venous leg ulcers are treated with compression therapy. Incompetent saphenous veins and tributaries are abolished if the deep venous system is patent. Occluded iliac veins are recanalised and stented, as possible. Refractory venous leg ulcers are grafted with split skin or punch grafts, depending on their surface. Extensive dermatolipofasciosclerosis may be tangentially removed by shave therapy or fasciectomy, that can be combined with negative pressure wound treatment (NPWT). Skin equivalents are an alternative to treat superficial venous leg ulcers that fail to epithelialise. Their indication in the treatment of more complex leg ulcers still needs to be better investigated and understood. The use of dermal matrices leads to more stable scars. Mixed venous-arterial leg ulcers heal slower and recur more frequently. Compression needs to be reduced. Refractory cases require arterial revascularisation, to transform the mixed venous-arterial into a venous leg ulcer. Arterial leg ulcers require arterial revascularization and split skin graft. Martorell hypertensive ischemic leg ulcer is still underrecognised and often confounded with with pyoderma gangrenosum, which leads therapy into a wrong direction. Necrosectomy, antibiotic treatment in the presence of relevant bacterial superinfection, and repeated split skin grafts eventually heal the vast majority of these extremely painful and potentially mortal wounds.

A case of tinea incognita and differential diagnosis of figurate erythema.

A patient with tinea incognita is presented together with a review of the literature of figurate erythema. Figurate lesions are emblematic for dermatology and perhaps the most picturesque efflorescences. The differential diagnosis can be broad and sometimes challenging. Many clinical entities with resembling primary and secondary efflorescences have to be considered as differentials and can be due to anti-infectious, paraneoplastic, allergic, autoimmune or other immune reactions.

Mucocutaneous Ulcerations and Pancytopenia due to Methotrexate Overdose.

Methotrexate (MTX) is an antifolic drug used in the treatment of immune-mediated and neoplastic diseases. Initiation or dosage changes in MTX therapy can cause mucositis and bone marrow suppression. Skin lesions due to acute MTX toxicity are rare, but they serve as a herald for later-onset pancytopenia. Therefore, identification of those cutaneous lesions might help to initiate rescue strategies at an early stage. Here we describe a case with mucocutaneous ulcerations and pancytopenia due to overdosed MTX.

Extreme Phenotype of Epidermal Growth Factor Receptor Inhibitor-induced Destructive Folliculitis.

Due to the increasingly widespread use and side effect profile of epidermal growth factor receptor inhibitors (EGFRIs), cutaneous side effects of these drugs are frequently encountered. The EGFR is expressed on keratinocytes and fibroblasts. Inhibition of EGFR can produce a range of cutaneous adverse effects, the most frequent being a characteristic acneiform skin eruption. As the latter is associated with good anti-neoplastic responses, the onset of EGFRI-induced acneiform skin eruption is typically viewed as a positive sign by patients and physicians. It can usually be treated well with standard acne drugs, but in rare cases, the skin eruption can be so severe that systemic therapy and/or interruption of EGFRI treatment are required. One of the severest forms of EGFRI-induced skin eruption occurring on the head and neck area resembles folliculitis decalvans. Here, we discuss the management of such a case seen in our department. In addition, we present an analysis of tumor necrosis factor-α, interleukin-1ß (IL-1ß), and IL-17A expression based on immunohistochemical stains and qPCR.

T-cell mediated anti-tumor immunity after photodynamic therapy: why does it not always work and how can we improve it?

Photodynamic therapy (PDT) uses the combination of non-toxic photosensitizers and harmless light to generate reactive oxygen species that destroy tumors by a combination of direct tumor cell killing, vascular shutdown, and activation of the immune system. It has been shown in some animal models that mice that have been cured of cancer by PDT, may exhibit resistance to rechallenge. The cured mice can also possess tumor specific T-cells that recognize defined tumor antigens, destroy tumor cells in vitro, and can be adoptively transferred to protect naïve mice from cancer. However, these beneficial outcomes are the exception rather than the rule. The reasons for this lack of consistency lie in the ability of many tumors to suppress the host immune system and to actively evade immune attack. The presence of an appropriate tumor rejection antigen in the particular tumor cell line is a requisite for T-cell mediated immunity. Regulatory T-cells (CD25+, Foxp3+) are potent inhibitors of anti-tumor immunity, and their removal by low dose cyclophosphamide can potentiate the PDT-induced immune response. Treatments that stimulate dendritic cells (DC) such as CpG oligonucleotide can overcome tumor-induced DC dysfunction and improve PDT outcome. Epigenetic reversal agents can increase tumor expression of MHC class I and also simultaneously increase expression of tumor antigens. A few clinical reports have shown that anti-tumor immunity can be generated by PDT in patients, and it is hoped that these combination approaches may increase tumor cures in patients.