Effectiveness of mogamulizumab in patients with Mycosis Fungoides or Sézary syndrome: A multicentre, retrospective, real-world French study.

BACKGROUND: Efficacy and safety of mogamulizumab, a monoclonal antibody directed against C-C chemokine receptor 4, were demonstrated in a previous multinational clinical trial conducted in patients with previously treated cutaneous T-cell lymphoma (CTCL): Sézary syndrome (SS) or Mycosis Fungoides (MF). OBJECTIVES: The real-world French OMEGA study aimed to describe effectiveness and tolerability of mogamulizumab in adult patients with CTCL, overall and according to the disease (SS or MF). METHODS: In this retrospective study, patients treated with mogamulizumab for SS or MF were included from 14 French expert centres. The overall response rate (ORR) under treatment was described (primary criterion), as well as treatment use and safety data. RESULTS: The 122 analysed patients (69 SS, 53 MF) were aged 66.6 ± 12.1 years at mogamulizumab initiation, and their median disease duration was 2.5 years (IQR: 1.3-5.6). Prior to treatment start, they received a median of three systemic CTCL therapies (2-5). Overall, 77.8% of patients suffered from advanced disease (Stage IIB-IVB), with frequent blood (B1/B2) involvement (67.5%). Over the treatment period (median: 4.6 months, 2.1-7.2), 96.7% of patients received all the planned mogamulizumab infusions. Among the 109 patients evaluable for effectiveness, ORR was 58.7% (95% CI [48.9-68.1]) overall, 69.5% [56.1-80.8] in SS and 46.0% [31.8-60.7] in MF. Compartmental response in the blood was observed in 81.8% [69.1-90.9] of SS patients. Skin responses were observed in 57.0% [47.0-66.5] of patients overall, 66.7% [52.9-78.6] in SS and 46.0% [31.8-60.7] in MF. The most common serious adverse drug reactions were rash (8.1% of patients) and infusion-related reactions (2.4%) which led to treatment discontinuation in 7.3% and 0.8% of patients, respectively. One patient with SS died from mogamulizumab-related tumour lysis syndrome. CONCLUSIONS: This large French study confirmed the effectiveness and tolerability of mogamulizumab in SS and MF patients in routine medical practice.

The value of five blood markers in differentiating mycosis fungoides and Sézary syndrome: a validation cohort.

BACKGROUND: Clinical and histological diagnosis of Sézary syndrome (SS) and mycosis fungoides (MF) is challenging in clinical routine. OBJECTIVES: We investigated five blood markers previously described for SS (T-plastin, Twist, KIR3DL2, NKp46 and Tox) in a prospective validation cohort of patients. METHODS: We included 447 patients in this study and 107 patients were followed up for prognosis. The markers were analysed by reverse transcriptase quantitative real-time polymerase chain reaction (RT-qPCR) on peripheral blood leucocytes and CD4+ T cells in a cohort of consecutive patients with early MF, erythrodermic MF and SS and compared with patients presenting with benign inflammatory dermatoses (BID) and erythrodermic BID. The markers were assessed in parallel to gold standard values such as CD4/CD8 ratio, loss of CD7 and CD26 membrane expression and CD4 absolute values. Sensitivity and specificity were analysed by receiver operator characteristic curves. The prognostic value of selected markers was analysed on a subset of patients. This study was conducted in one centre. RESULTS: We defined cut-off values for each marker. T-plastin, Twist and KIR3DL2 had the best validity. SS may be overrepresented. The combination of T-plastin and Twist was able to differentiate between erythrodermic MF or BID and SS. The additional analysis of KIR3DL2 may be useful to predict the prognosis. CONCLUSIONS: We propose T-plastin, Twist and KIR3DL2 measured by RT-qPCR as new diagnostic markers for Sézary syndrome.

Epidemiological changes in cutaneous lymphomas: an analysis of 8593 patients from the French Cutaneous Lymphoma Registry.

BACKGROUND: Primary cutaneous lymphomas (PCLs) are a heterogeneous group of T-cell (CTCL) and B-cell (CBCL) malignancies. Little is known about their epidemiology at initial presentation in Europe and about potential changes over time. OBJECTIVES: The aim of this retrospective study was to analyse the frequency of PCLs in the French Cutaneous Lymphoma Registry (GFELC) and to describe the demography of patients. METHODS: Patients with a centrally validated diagnosis of primary PCL, diagnosed between 2005 and 2019, were included. RESULTS: The calculated incidence was unprecedently high at 1·06 per 100 000 person-years. The number of included patients increased yearly. Most PCL subtypes were more frequent in male patients, diagnosed at a median age of 60 years. The relative frequency of rare CTCL remained stable, the proportion of classical mycosis fungoides (MF) decreased, and the frequency of its variants (e.g. folliculotropic MF) increased. Similar patterns were observed for CBCL; for example, the proportion of marginal-zone CBCL increased over time. CONCLUSIONS: Changes in PCL frequencies may be explained by the emergence of new diagnostic criteria and better description of the entities in the most recent PCL classification. Moreover, we propose that an algorithm should be developed to confirm the diagnosis of PCL by central validation of the cases.

Actinic cheilitis: a systematic review of treatment options.

Actinic cheilitis is a premalignant condition that can progress to squamous cell carcinoma with a higher propensity for metastasis than cutaneous squamous cell carcinoma. Optimal treatment for actinic cheilitis has not been established, and evidence-based estimates of clinical cure in the dermatology literature are limited. Here, we review and synthesize outcome data published for patients with actinic cheilitis after treatment with various modalities. A systematic review was conducted in MEDLINE, Embase and the Cochrane library for English, French and German-language studies and references of included articles from inception to 20 January 2020. Studies were included if they reported on at least six patients with biopsy-proven actinic cheilitis. After quality appraisal, results of studies with the strongest methodology criteria were synthesized. 18 studies of 411 patients (published 1985 to 2016) were included. The majority of the studies were case series. Carbon dioxide laser ablation and vermilionectomy were associated with the most favourable outcomes with fewest recurrences. Chemical peel and photodynamic therapy were associated with higher recurrence. Adverse effects generally resolved in the weeks following treatment and cosmetic outcomes were favourable overall. In conclusion, there is a lack of high-quality comparative studies evaluating different treatment options for actinic cheilitis. The included publications used various outcome measures; however, the majority reported on the recently defined core outcome sets. These results suggest that both carbon dioxide laser ablation and vermilionectomy are effective treatments for actinic cheilitis. Prospective head-to-head studies are needed to compare these treatment modalities and to assess patient preferences.

Does dietary fluid intake affect skin hydration in healthy humans? A systematic literature review.

BACKGROUND: Associations between daily amounts of drinking water and skin hydration and skin physiology receive increasingly attention in the daily life and in clinical practice. However, there is a lack of evidence of dermatological benefits from drinking increased amounts of water. MATERIALS AND METHODS: Pubmed and Web of Science were searched without any restrictions of publication dates. References of included papers and related reviews were checked. Eligibility criteria were primary intervention and observational studies investigating the effects of fluid intake on skin properties in English, German, Spanish or Portuguese language, including subjects being healthy and 18+ years. RESULTS: Searches resulted in 216 records, 23 articles were read in full text, and six were included. The mean age of the samples ranged from 24 to 56 years. Overall the evidence is weak in terms of quantity and methodological quality. Disregarding the methodological limitations a slight increase in stratum corneum and "deep" skin hydration was observed after additional water intake, particularly in individuals with lower prior water consumption. Reductions of clinical signs of dryness and roughness were observed. The extensibility and elasticity of the skin increased slightly. Unclear associations were shown between water intake and transepidermal water loss, sebum content, and skin surface pH. CONCLUSIONS: Additional dietary water intake may increase stratum corneum hydration. The underlying biological mechanism for this possible relationship is unknown. Whether this association also exists in aged subjects is unclear. Research is needed to answer the question whether increased fluid intake decreases signs of dry skin.

Evidence-based (S3) guideline for the treatment of androgenetic alopecia in women and in men - short version.

Androgenetic alopecia is the most common hair loss disorder, affecting both men and women. Initial signs of androgenetic alopecia usually develop during teenage years leading to progressive hair loss with a pattern distribution. Moreover, its frequency increases with age and affects up to 80% Caucasian men and 42% of women. Patients afflicted with androgenetic alopecia may undergo significant impairment of quality of life. The European Dermatology Forum (EDF) initiated a project to develop evidence-based guidelines for the treatment of androgenetic alopecia. Based on a systematic literature research the efficacy of the currently available therapeutic options was assessed and therapeutic recommendations were passed in a consensus conference. The purpose of the guideline is to provide dermatologists with an evidence-based tool for choosing an efficacious and safe therapy for patients with androgenetic alopecia.

[Intra-arterial procaine injection in peripheral arterial disease]. / Intraarterielle Procaingabe bei peripherer arterieller Verschlusskrankheit.

The report concerns a 61-year-old woman suffering from a chronic pain syndrome of peripheral arterial vascular disease. Despite level III-WHO medication she was not able to walk a distance of more than 100 m without pain. The patient received sonographically guided procaine injections into both femoral arteries. Directly after the injection the patient was free of pain for 4 weeks and for 6 months after a repeat injection.

[Herbal medicines for psychiatric disorders]. / Phytotherapie bei psychiatrischen Erkrankungen.

BACKGROUND: In Germany herbal medicines are traditionally frequently used. They represent an important therapeutic option, especially in self-medication. METHODS: Current systematic review articles and meta-analyses were evaluated and summarized with respect to the evidence of phytotherapeutic drugs for selected psychiatric indications. RESULTS: Apart from the use of St. John's wort for depression, no other herb has so far shown convincing evidence. CONCLUSION: Due to the promising effects and the low side effect potential within the existing studies, further randomized controlled trials (e. g. for Passiflora incarnata, Rhodiola rosea and Lavendula officinalis) are definitely indicated.

Sensitivity to change of the Dermatology Life Quality Index in adult females with facial acne vulgaris: a validation study.

BACKGROUND: The postadolescent form of acne papulopustulosa, also referred to as 'acne tarda' can have substantial negative impact on Quality of Life, especially in adult female patients. OBJECTIVE: Although the Dermatology Life Quality Index (DLQI) is widely used, empirical evidence about its performance in adult female acne patients is lacking. METHODS: In this prospective cohort study, we have investigated the sensitivity to change of the DLQI in 53 female adult acne patients with mild to moderate facial acne treated with azelaic acid (AzA) 15% gel twice daily over 24 weeks. RESULTS: Mean Investigator Static Global Assessment (ISGA) score was 2.3 (SD 0.5) at baseline and ranged from 0.9 (SD 0.3) to 2.1 (SD 0.4) at the end of the study in the 'Highly Improved' and 'Unchanged' responder groups respectively. The mean baseline DLQI score was 5.1 (SD 4.2). The Effect Size in the responder group 'Highly Improved' was 0.66; in group 'Improved' 0.62 and 0.23 in group 'Unchanged'. At the end of study, the mean DLQI score ranged from 1.1 (SD 1.5) in the 'Highly Improved' group to 3.7 (SD 6.0) in the 'Unchanged' group. CONCLUSION: The results support the sensitivity to change of the DLQI in this population.

Effects of two different fabrics on skin barrier function under real pressure conditions.

BACKGROUND: Pressure Ulcers (PUs) are a severe form of skin and soft tissue lesions, caused by sustained deformation. PU development is complex and depends on different factors. Skin structure and function change during prolonged loading on PU predilection sites and surfaces being in direct contact with skin are likely to have an impact as well. Little is known about the influence of fabrics on skin function under pressure conditions. OBJECTIVES: To investigate skin responses to sustained loading in a sitting position and possible differences between two fabrics. METHODS: Under controlled conditions 6 healthy females (median age 65.0 (61.0-67.8) years) followed a standardized immobilization protocol of a sitting position for 45 min on a spacer and on a cotton fabric. Before and after the loading period skin surface temperature, stratum corneum hydration, transepidermal water loss (TEWL), erythema, skin elasticity and 'relative elastic recovery' were measured at the gluteal areas. RESULTS: A 45 min sitting period caused increases of skin surface temperature and erythema independent of the fabric. Loading on spacer fabric showed a two times higher increase of TEWL compared to cotton. Stratum corneum hydration showed slight changes after loading, skin elasticity and 'relative elastic recovery' remained stable. CONCLUSIONS: Sitting on a hard surface causes skin barrier changes at the gluteal skin in terms of stratum corneum hydration and TEWL. These changes are influenced by the fabric which is in direct contact to the skin. There seems to be a dynamic interaction between skin and fabric properties especially in terms of temperature and humidity accumulation and transport.

Follicular fluorescence quantity to characterize acne severity: a validation study.

BACKGROUND: Porphyrins are native fluorophores in the follicle openings, visible under ultraviolet-A light. Acne severity might be associated with increased Propionibacterium acnes colonization and porphyrin production. Aim of this study was to investigate whether the parameter fluorescence quantity can be used to measure acne severity. METHODS: A validation study was conducted in 24 patients with acne using split-face design. Acne severity was measured using Investigator Static Global Assessment scores and lesion counts. Reliability, construct validity and sensitivity to change in fluorescence quantity were investigated. RESULTS: Mean baseline Investigator Static Global Assessment score was 2.7 (SD 0.1). Mean baseline fluorescence quantities were 24.8 (SD 4.0) on the cheek and 20.3 (SD 4.6) on the chin. On day 25, values ranged from 6.0 (SD 6.0) to 18.1 (SD 18.4) on the cheek and from 2.6 (SD 4.4) to 14.7 (SD 16.2) on the chin. The intraclass correlation coefficients of fluorescence quantity ranged from 0.513 to 0.987. Effect sizes for fluorescence measurements were highest on the chin and cheek ranging from 0.24 to 0.77 and 0.32 to 0.75, respectively. CONCLUSION: Fluorescence quantity indicates acne severity, especially on the inner cheek and chin areas. Fluorescence quantity is reliable but is not as sensitive as manual lesion counting.

Evaluation of skin ageing: a systematic review of clinical scales.

Clinical scales are widely used in anti-ageing research and practice. More than 100 skin ageing scales exist, which makes it difficult to choose outcome measures and to compare study results. The objectives were to assess and evaluate the quality of measurement properties of available clinical skin ageing scales. A systematic review was conducted. Electronic databases including Medline (1970 to June 2013) and EMBASE (1974 to June 2013) were searched via Ovid SP. To enhance the sensitivity forward searches were conducted in Scopus and Web of Science. We identified 111 scales in 52 included publications. Thirty studies had good methodology for at least one measurement property. Forty-two scales were evaluated for their test-retest or interrater reliability. Nineteen showed high reliability coefficients. A further 15 instruments were partly supported by content and/or structural and/or criterion validity and/or hypotheses-testing evidence. The majority of existing clinical skin ageing scales were developed for evaluating facial characteristics. Many scales quantify similar constructs. In contrast to the high number of available scales there is limited evidence supporting their measurement properties. Recommendations for the use of specific skin ageing scales for clinical studies must be made with caution because of the high number of studies with poor methodology. Development of new instruments should be justified, and existing ones investigated for scale behaviour using appropriate methods. Future research should aim to select and/or adapt existing scales to identify the 'best' to improve clinical research and practice.

Reliability and validity of two in vivo measurements for skin surface topography in aged adults.

BACKGROUND: The non-contact optical methods phaseshift rapid in vivo measurement of skin (PRIMOS) and surface evaluation of living skin (SELS) are widely applied for measuring skin surface topography. The aims of the present study were to evaluate reliability and validity of these methods and to compare skin roughness intraindividually. METHODS: SELS and PRIMOS measurements were performed on four skin areas of the left and right volar forearms in 12 healthy elderly subjects. Reliability and correlations were analyzed for Visioscan® and PRIMOS roughness parameters. Student's t-tests for estimating differences between contralateral volar forearm sites were applied. RESULTS: ICC coefficients of the Visioscan® roughness estimates ranged between 0.50 and 0.95 and of the PRIMOS measurements between 0.01 and 1.00. The Visioscan® parameters SEr, SEsm, Rmax, and Rz, and the PRIMOS parameters Ra, Rz, Smax, Wt, and Sz showed most significant correlations with each other and to additional roughness parameters. Mean roughness differences between contralateral forearm skin areas ranged between 0.0 (SEsc) and 6.7 (Rmax). CONCLUSIONS: The Visioscan® parameters SEr, Rmax, and Rz showed most reliable and valid values and were largely comparable on contralateral forearm skin sites in elderly subjects. Rmax, Rz, and Ra should be preferred for measuring skin surface topography with PRIMOS.

Relation between skin micro-topography, roughness, and skin age.

BACKGROUND: The topography of the skin surface consists of lines, wrinkles, and scales. Primary and secondary lines form a network like structure that may be identified as polygons. Skin surface roughness measurements are widely applied in dermatological research and practice but the relation between roughness parameters and their anatomical equivalents are unclear. This study aimed to investigate whether the number of closed polygons (NCP) per measurement field can be used as a reliable parameter to measure skin surface topography. For this purpose, we analysed the relation between skin surface roughness parameters and NCP in different age groups. METHODS: Images of the volar forearm skin of 38 subjects (14 children, 12 younger, and 12 older adults) were obtained with the VisioScan VC98. The NCP was counted by three independent researchers and selected roughness parameters were measured. Interrater reliability of counting the number of closed polygons and correlations between NCP, roughness parameters, and age were calculated. RESULTS: The mean NCP/mm² in children was 3.1 (SD 1.1), in younger adults 1.0 (SD 0.7), and in older adults 1.0 (SD 0.9). The interrater reliability was 0.9. A negative correlation of NCP/mm² with age was observed, whereas measured roughness parameters were positively associated with age. NCP/mm² was weakly related to skin roughness. CONCLUSION: The NCP/mm² is a reproducible parameter for characterizing the skin surface topography. It is proposed as an additional parameter in dermatological research and practice because it represents distinct aspects of the cutaneous profile not covered by established roughness parameters.

Quantifying dyspigmentation in facial skin ageing: an explorative study.

OBJECTIVE: The skin melanin system is affected by ageing, resulting in dyspigmentation with associated clinical and psychosocial consequences. In dark skinned phenotypes, broad evidence is available, whereas little is known about pigmentary changes in fair-skinned Caucasians. The objective of this study was to investigate age-related changes in facial pigmentation and dyspigmentation in subjects of skin phototypes II-III and to develop and test parameters for quantifying dyspigmentation. METHODS: Twenty-four skin healthy female subjects were recruited in three distinct age groups (30-40, 50-60, 70-80 years). Skin colour was measured by Mexameter and Chromameter. Skin dyspigmentation was measured by clinical evaluation and newly developed image-processing parameters on the cheeks and the forehead. The reliability of the clinical evaluation was investigated by intraclass correlation coefficients between three raters, and the validity of the dyspigmentation parameters was analysed by bivariate correlations with related measures. RESULTS: Skin lightness decreased with increasing age. Clinical dyspigmentation scores showed positive associations with chronological age ranging between 0.452 and 0.606. RBX(®) -Brown transformation-based hyperpigmentation and hypopigmentation indices increased with age, whereas the overall pigmentation intensity decreased with age at the cheeks. The image analysis-based parameters showed strong associations with the clinical scores and related measurements. CONCLUSION: We demonstrated age-related changes in the facial colour and dyspigmentation of fair-skinned Caucasian females. An increase in dyspigmentation was found by clinical scoring and the RBX(®) -Brown transformation-based pigmentation indices. The validity of hyper- and hypopigmentation indices and overall pigmentation intensity was supported. The RBX(®) transformation-based pigmentation indices might be applied in future studies to complement or substitute clinical evaluation.

Using ultrasound elastography to monitor human soft tissue behaviour during prolonged loading: A clinical explorative study.

PURPOSE: Pressure ulcers are localized injuries to the skin or underlying tissues over a bony prominence, as a result of pressure, or pressure in combination with shear. Ultrasound imaging techniques are widely applied to detect and to investigate pressure ulcer pathogenesis and healing, but due to missing structural alterations, very early signs of tissue alterations are not detectable. Ultrasound elastography was proposed as a new method to measure very early signs of pressure ulcer development but this was not investigated in humans so far. The aim of this study was to investigate for the first time whether US elastography is able to measure potential changes in dermal and subcutaneous tissue stiffness during prolonged loading. MATERIALS AND METHODS: An exploratory study including nine healthy volunteers (mean age 70.1 (SD 4.8) years) was conducted. Study participants were requested to follow a standardized lying protocol, consisting of two loading phases of 90 and 150 min in supine position on a standard hospital mattress. Three pressure ulcer predilection sites (lateral heel over the calcaneus, sacral, and upper back area) were measured using B-mode and elastographic ultrasound system at baseline - immediately, after 90 min, and after 150 min loading. RESULTS: Mean baseline shear wave velocities were highest in the heel skin (2.7 m/s) and lowest in the upper back skin (1.9 m/s) indicating that heel skin was stiffest. Also the subcutaneous soft tissue stiffness was highest for the heel (2.7 m/s) and lowest for the upper back region (1.3 m/s). After 90 and 150 min loading there was a mean stiffness increase of the skin layers and a pronounced stiffness decrease of subcutaneous heel and sacral tissues. CONCLUSIONS: Continuous loading of skin and underlying subcutaneous soft tissues leads to dynamic changes of tissue stiffness which are considered to play key roles in pressure ulcer development. Superficial skin and deep tissues seem to react differently. Elastography is able to quantify the dynamic of skin and subcutaneous soft tissue stiffness changes non-invasively in vivo. Shear wave velocity might serve as a new parameter for quantifying pressure ulcer damage risk in superficial and deeper tissues prone to pressure ulcer development.

Skin response to sustained loading: A clinical explorative study.

BACKGROUND: Severe illness, disability and immobility increase the risk of pressure ulcer development. Pressure ulcers are localized injuries to the skin and/or underlying tissue as a result of long enduring pressure and shear. Little is known about the role of the stratum corneum and the upper skin layers in superficial pressure ulcer development. OBJECTIVES: To investigate possible effects of long enduring loading on the skin barrier function under clinical conditions at two pressure ulcer predilection sites. METHODS: Under controlled conditions 20 healthy females (mean age 69.9 (3.4) years) followed a standardized immobilization protocol of 90 and 150 min in supine position wearing hospital nightshirts on a standard hospital mattress. Before and immediately after the loading periods skin surface temperature, stratum corneum hydration, transepidermal water loss and erythema were measured at the sacral and heel skin. RESULTS: Prolonged loading caused increases of skin surface temperature and erythema at the sacral and heel skin. Stratum corneum hydration remained stable. Transepidermal water loss increased substantially after loading at the heel but not at the sacral skin. CONCLUSIONS: Skin functions change during prolonged loading at the sacral and heel skin in aged individuals. Accumulation of heat and hyperaemia seem to be primarily responsible for increasing skin temperature and erythema which are associated with pressure ulcer development. Increased transepidermal water loss at the heels indicate subclinical damages of the stratum corneum at the heel but not at the sacral skin during loading indicating distinct pathways of pressure ulcer development at both skin areas.