Surgery followed by 585 nm pulsed-dye laser therapy in the treatment of granuloma faciale.

Granuloma faciale is a rare, benign skin disease characterised by solitary or multiple papules, plaques or nodules, most often occurring on the face. The skin disorder is often associated with exacerbations and remissions; spontaneous resolution seldom occurs. The treatment of granuloma faciale is challenging. Various topical and systemic treatments, but also surgical and laser therapies have been administered. A spatially confined thermal destruction of the tissue is achieved by strong absorption of haemoglobin at 585 nm wavelength. Of note, none of the presently available therapeutic interventions are particularly successful. Moreover, Granuloma faciale has the tendency to recur after treatment. Here, we present a male patient with a treatment refractory Granuloma faciale on the right cheek who was successfully treated with the combination of surgery and pulsed-dye laser therapy. Besides the good aesthetic outcome, remission was maintained after almost 1 year of follow-up.

Effect of obesity on venous blood flow in the lower limbs.

BACKGROUND AND OBJECTIVES: Although obesity is a recognized risk factor for the development of lower limb venous disease, less attention has been paid to objectively measuring the effect of centripetal obesity on blood flow in the lower limbs. PATIENTS AND METHODS: The diameter of lower limb veins and venous blood flow were measured in 44 patients (65.6 ± 12.5 years, 25 females, 19 males) with centripetal obesity and chronic venous disease. RESULTS: The mean diameter of both common femoral veins (CFV) increased significantly in the semi-supine position following elevation of the panniculus (right: ∆0.73 ± 1.21 mm; p ≤ 0.001, left: ∆1.16 ± 1.42 mm; p ≤ 0.001). Moreover, there was a significant increase in venous flow volume in the left CFV (∆62.96 ± 117.85 ml/min; p  =  0.001). Similarly, there was an increase in the diameter of left great saphenous vein (∆0.24 ± 0.41 mm; p  =  0.002), measured at the mid-thigh, when the patient lifted their abdominal panniculus. Finally, the grade of obesity correlated with the extent of the venous disease. CONCLUSIONS: These data provide preliminary evidence that centripetal obesity results in both structural and hemodynamic changes in the lower limb veins, even in the absence of classical reflux.

[Postthrombotic syndome-a complex clinical picture]. / Postthrombotisches Syndrom ­ ein komplexes Krankheitsbild.

Postthrombotic syndrome (PTS), which comprises a range of symptoms and signs following the development of deep vein thrombosis, is associated with varied clinical presentation. The functional limitations associated with PTS may be persistent, and following deep vein thrombosis, the patient may require lifelong anticoagulation. Venous ulceration is often regarded as a complication of PTS. However, the development of venous ulceration strictly depends on underlying venous hypertension, which is not always present. Due to the heterogenous clinical presentation of PTS, diagnosis may be difficult. Nevertheless, accurate diagnosis is vital and modern imaging techniques can help establish the diagnosis and play a role in monitoring treatment response. Thus, in addition to new strategies in compression therapy, (endo)vascular interventions are established treatment modalities in the management of PTS.

S1 guideline: Differential diagnosis of acute and chronic redness of the lower legs.

Acute or chronic redness of the lower leg is a frequent reason for visits to clinics and practices. The differential diagnosis is often challenging. The aim of this guideline is to define criteria and procedures for the differential diagnosis of acute or chronic, unilateral or bilateral redness of the lower leg. Finding the correct diagnosis is essential for selecting an appropriate treatment and can help to reduce the inappropriate use of antibiotics. The guideline committee identified the most relevant differential diagnoses: 1. erysipelas, 2. stasis dermatitis, 3. hyperergic ictus reaction, 4. superficial and deep vein thrombosis, 5. gout, 6. chronic allergic contact dermatitis, and 7. acute toxic or allergic contact dermatitis. Algorithms/diagnostic pathways, each of which can be broken down into anamnesis, clinical examination, and diagnostics, have been developed for these seven diagnoses. In addition, the guideline group identified over 40 other relevant diagnoses and summarized their characteristics in a table to facilitate further differential diagnoses.

Clinical outcome of short-term compression after sclerotherapy for telangiectatic varicose veins.

BACKGROUND: Sclerotherapy is considered to be the method of choice for the treatment of telangiectatic varicose veins (C1 veins). Whereas the use of compression stockings after sclerotherapy is recommended, little is known about the impact of compression on the outcome of sclerotherapy. The aim of this study was to assess the influence of compression on the outcome of injection sclerotherapy of C1 varicose veins. METHODS: There were 100 legs of 50 consecutive patients with chronic venous insufficiency (C1) included. After randomization per patient, both legs were treated with sclerotherapy in a predefined area of the thigh (measuring 100 cm2), followed by eccentric compression for 24 hours. Group A received no further compression, whereas group B was additionally equipped with compression stockings of 18 to 20 mm Hg above the ankle and continued wearing these for 1 week. Photodocumentation was performed before, 1 week after, and 4 weeks after sclerotherapy, and the clinical outcome was assessed at these postprocedure follow-up dates. The photographs were reviewed by an internal unblinded rater and an independent blinded external rater. RESULTS: There was no discernible difference between the groups in terms of clinical outcome or side effects after 4 weeks. Whereas inter-rater reliability was high, there was no correlation between the raters and patients in terms of outcome. In 55% of the treated legs, the patients deemed the result of the treatment to be good; in 27% of the treated legs, fair; and in 18%, poor. Postprocedure hyperpigmentation occurred in 13% of patients and was comparable in both groups. Compression therapy was found to be comfortable by the majority (58%) of patients. CONCLUSIONS: One week of postinterventional compression therapy had no clinical benefit compared with no compression.

The Role of the Cutaneous Microbiome in Hidradenitis Suppurativa-Light at the End of the Microbiological Tunnel.

The development of next generation sequencing, coupled with advances in bio-informatics, has provided new insights into the role of the cutaneous microbiome in the pathophysiology of a range of inflammatory skin diseases. In fact, it has even been suggested that the identification of specific skin microbial signatures may not only be useful in terms of diagnosis of skin diseases but they may also ultimately help inform personalised treatment strategies. To date, research investigating the role of microbiota in the development of inflammatory skin diseases has largely focused on atopic eczema and psoriasis vulgaris. The role of the microbiome in Hidradenits suppurativa (HS)-also known as acne inversa-a chronic auto-inflammatory skin disease associated with significant morbidity, has received comparatively little attention. This is despite the fact that antimicrobial therapy plays a central role in the treatment of HS. After briefly outlining the clinical features of HS and current treatment strategies, we move on to review the evidence of microbial dysbiosis in HS pathophysiology. We conclude by outlining the potential for metagenomic studies to deepen our understanding of HS biology but more importantly to identify novel and much needed treatment strategies.

[Modern treatment of varicose veins]. / Moderne Behandlungsverfahren der Varikose der unteren Extremität.

Varicosis of the lower limb is a common disease that can lead to edema, trophic disturbances and skin ulcerations. In addition to the classic surgical procedure of crossectomy with stripping of the saphenous vein, a growing number of minimally invasive endoluminal treatment methods has been established over the past 15 years, offering a colorful array of procedures to the modern phlebologist. It is important to choose the optimal treatment option for each individual patient.

Comparison of Four Haemodynamic Tests that Quantify Superficial Venous Insufficiency.

OBJECTIVES: Reflux assessment with ultrasound (U/S) is usually qualitative. Quantitative measurements of superficial venous insufficiency (SVI) include the venous arterial flow index (VAFI), recirculation index (RCI), venous filling index (VFI), and the postural diameter change (PDC) of the saphenous trunk. The aim was to investigate their relationship. MATERIALS AND METHODS: This was an observational study performed on patients with varicose veins and hospital employees. Four haemodynamic parameters were measured in 21 legs from 16 subjects. Legs were divided into no reflux (n = 7) and reflux (n = 14). The VAFI is the U/S ratio of common femoral vein volume flow divided by the common femoral artery volume flow, performed supine. The RCI is the U/S ratio of reflux volume over antegrade volume within the saphenous trunk after calf compression, standing. The VFI is the rate of calf volume increase on dependency measured in mL/s, using air plethysmography. The PDC is the percentage reduction of the saphenous trunk diameter from standing to lying, using U/S. RESULTS: The clinical part of the CEAP classification was: C0 = 3, C1 = 4, C2 = 5, C3 = 1, C4a = 1, C4b = 6, C5 = 1. All four tests demonstrated significant differences between the two groups with minimal overlap (Mann Whitney U test): VAFI (p = .028), RCI (p < .0005), VFI (p = .001), and PDC (p = .014). Furthermore, significant correlations were observed with the tests: VAFI vs. RCI (r = .532, p = .015), VFI (r = .489, p = .025) and PDC (r = -.474, p = .030); RCI vs. VFI (r = .446, p = .043) and PDC (r = -.527, p = .014). CONCLUSIONS: Superficial venous drainage insufficiency should not be confined to an U/S assessment of the presence of reflux, which is qualitative. Quantitative data may be provided using the VAFI, RCI, VFI, and PDC. Understanding why there are significant correlations among these parameters and the preferred objective reference test requires further work.

Transient increased tumescence of the glans penis during penile erection after endovenous ablation of the great saphenous vein.

OBJECTIVE: The primary objective of our study was to investigate the impact of endovenous ablation of the great saphenous vein (GSV) on the degree of tumescence of the glans penis during penile erection as well as on global erectile function (EF). METHODS: We included patients scheduled for one of three different methods of endoluminal treatment. Our questionnaire was composed of the EF domain of the International Index of Erectile Function, an additional question that has been validated for assessment of swelling (tumescence) of the glans penis, and a question on the use of erectogenic medication. RESULTS: There were 62 patients enrolled in the study. Seven patients (11%) reported a postoperative enlargement of the glans penis on penile erection compared with the subjectively assessed glans tumescence before surgery. Three patients (5%) reported an increased tumescence of the glans 1 week after surgery, and four (7.4%) different patients reported the effect 3 months after surgery. Of these seven men, three had normal EF (score ≥26) at any time. One patient had mild erectile dysfunction before the operation, with an improvement to normal EF from week 1 throughout the observation in the study (3 months). CONCLUSIONS: This is the first prospective study that confirms an unexpected side effect of endoluminal treatment of the GSV occurring in approximately 10% of men. It might be of interest for insufficient responders to phosphodiesterase type 5 inhibitors with varicosis of the GSV in the future.

Giant congenital melanocytic nevus with vascular malformation and epidermal cysts associated with a somatic activating mutation in BRAF.

Giant congenital melanocytic nevi may be symptomatically isolated or syndromic. Associations with capillary malformations are exceptional, and development of epidermal cysts has not been described. A 71-year-old patient with a giant congenital melanocytic nevus (CMN) of the lower back, buttocks, and thighs was asymptomatic except for unexpected hemorrhage during partial surgical excision years before. Blunt trauma at age 64 initiated recurrent, severe pain under the nevus; multiple large epidermal cysts then developed within it. Imaging and biopsy showed a large, non-pulsatile venous malformation intermingled with the deep nevus. A low-abundance, heterozygous BRAF c.1799T>A (p.V600E) mutation was present in both gluteal and occipital congenital nevi; additional mutations in NRAS, GNAQ, GNA11, HRAS, or PIK3CA were undetectable. This is the first demonstration of a recurrent BRAF mutation in multiple large congenital nevi from the same individual, confirming that this malformation can have multiple genetic origins. Early constitutive activation of BRAF can therefore cause unusual associations of giant nevi with vascular malformations, indicating that both pigment and endothelial cell physiology may be affected by mosaic RASopathies.

The Extracellular Matrix Signature in Vein Graft Disease.

BACKGROUND: Vein graft disease is a major and yet unsolved problem in cardiac revascularization surgery. Although accumulation of extracellular matrix is characteristic for vein graft disease, detailed analysis of the fibrotic material is lacking. Because alterations of collagen cross-links are typical for organ fibrosis, we performed a comprehensive analysis of collagen and elastin in vein graft disease. METHODS: Collagen, elastin, and their respective cross-links were analyzed using histology and amino acid analysis. The expression of collagen-modifying enzymes was analyzed using SYBR Green quantitative real-time polymerase chain reaction. Fibrillin expression was analyzed by immunohistochemistry and quantitative real-time polymerase chain reaction. RESULTS: Diseased vein grafts showed a marked increase of collagen and of intermediate collagen cross-links, which are markers for newly synthesized collagen. Furthermore, we identified in vein graft disease increased levels of mature hydroxylysine aldehyde-derived cross-links typical for skeletal tissues. This was accompanied by upregulation of lysyl hydroxylase 2 and lysyl oxidase expression. Furthermore, vein graft disease showed a reduction of the elastin/collagen ratio, using elastin cross-links as a marker of elastin content, which was accompanied by an increase of fibrillin-1. CONCLUSIONS: Vein graft disease was accompanied by marked alterations in the composition of the extracellular matrix. The altered collagen cross-link pattern and the reduced elastin/collagen ratio might synergistically increase the stiffness in diseased vein grafts. Furthermore, hydroxylysine aldehyde-derived cross-links can cause a decreased degradability of collagens by matrix-metalloproteinases. Our data suggest collagen cross-links as a therapeutic target in vein graft disease.

Anticoagulation with rivaroxaban for livedoid vasculopathy (RILIVA): a multicentre, single-arm, open-label, phase 2a, proof-of-concept trial.

BACKGROUND: Livedoid vasculopathy is a thrombotic skin disease characterised by recurrent occlusion of the cutaneous microcirculation in lower extremities, which results in skin infarctions with painful ulcerations and irreversible scar formation. Rivaroxaban is a direct factor Xa inhibitor that prevents thrombus formation. We investigated whether rivaroxaban is effective for the treatment of livedoid vasculopathy. METHODS: We did this single-arm, open-label, multicenter, phase 2a, proof-of concept trial at three university hospitals in Germany. Patients with livedoid vasculopathy and a minimum pain score of 40 on the visual analogue scale were eligible to participate. Patients received oral rivaroxaban tablets for 12 weeks at an initial dose of 10 mg twice per day, which was reduced to once per day if a reduction of pain by 50% on the visual analogue scale was achieved. Subcutaneous enoxaparin at 1 mg per kg bodyweight once or twice per day was allowed as a backup treatment in case of insufficient efficacy and increased pain. The primary endpoint was change in pain on the visual analogue scale from baseline to 12 weeks. Efficacy was assessed in the intention-to-treat population and safety was assessed in all patients who received at least one dose of study drug. This trial is registered with the EU Clinical Trials Register, EudraCT number 2012-000108-13-DE, and is closed to new participants. FINDINGS: Between Dec 28, 2012, and April 24, 2014, 36 patients were screened, 28 patients were recruited for the study, and 25 patients received treatment. During treatment, five patients dropped out of the study because of withdrawal of consent (one patient), lack of compliance (one patient), violation of inclusion criteria (two patients), and a serious adverse event (one patient). Median pain on the visual analogue scale decreased from 65·0 (IQR 52·0-78·0) at baseline to 6·0 (1·0-14·0) after 12 weeks of treatment (p<0·0001). Six of the 20 patients required additional treatment with enoxaparin. Eight treatment-related adverse events were recorded in six (24%) of the 25 patients: five cases of menorrhagia including one classified as both menorrhagia and dysmenorrhoea, one case of dyspnoea, and one case of gingival bleeding. The only serious adverse reaction to rivaroxaban during the study was one case of menorrhagia in a patient with concomitant endometriosis, which resulted in study discontinuation. INTERPRETATION: Rivaroxaban seems to effectively reduce pain in livedoid vasculopathy. Therefore we suggest that rivaroxaban with enoxaparin as a backup treatment is a suitable treatment option for patients with livedoid vasculopathy. FUNDING: Deutsche Forschungsgemeinschaft and Bayer Vital.