In vitro effects of wound-dressings on key wound healing properties of dermal fibroblasts.

Healing of complex wounds requires dressings that must, at least, not hinder and should ideally promote the activity of key healing cells, in particular fibroblasts. This in vitro study assessed the effects of three wound-dressings (a pure Ca2+ alginate: Algostéril®, a Ca2+ alginate + carboxymethylcellulose: Biatain alginate® and a polyacrylate impregnated with lipido-colloid matrix: UrgoClean®) on dermal fibroblast activity. The results showed the pure calcium alginate to be non-cytotoxic, whereas the other wound-dressings showed moderate to strong cytotoxicity. The two alginates stimulated fibroblast migration and proliferation, whereas the polyacrylate altered migration and had no effect on proliferation. The pure Ca2+ alginate significantly increased the TGF-ß-induced fibroblast activation, which is essential to healing. This activation was confirmed by a significant increase in Vascular endothelial growth factor (VEGF) secretion and a higher collagen production. The other dressings reduced these fibroblast activities. The pure Ca2+ alginate was also able to counteract the inhibitory effect of NK cell supernatants on fibroblast migration. These in vitro results demonstrate that tested wound-dressings are not equivalent for fibroblast activation. Only Algostéril was found to promote all the fibroblast activities tested, which could contribute to its healing efficacy demonstrated in the clinic.

Consensus statement on the diagnosis and treatment of sclerosing diseases of the skin, Part 1: Localized scleroderma, systemic sclerosis and overlap syndromes.

The term 'sclerosing diseases of the skin' comprises specific dermatological entities, which have fibrotic changes of the skin in common. These diseases mostly manifest in different clinical subtypes according to cutaneous and extracutaneous involvement and can sometimes be difficult to distinguish from each other. The present consensus provides an update to the 2017 European Dermatology Forum Guidelines, focusing on characteristic clinical and histopathological features, diagnostic scores and the serum autoantibodies most useful for differential diagnosis. In addition, updated strategies for the first- and advanced-line therapy of sclerosing skin diseases are addressed in detail. Part 1 of this consensus provides clinicians with an overview of the diagnosis and treatment of localized scleroderma (morphea), and systemic sclerosis including overlap syndromes.

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.

"African" acral keratoderma: Further evidence for a single entity. A retrospective study of 42 patients.

BACKGROUND: Several phenotypes of non-inflammatory palmar and plantar keratoderma (PPK) have been described in patients of Sub-Saharan African descent. They include keratosis punctata of the palmar creases, marginal keratoderma, also known as acrokeratoelastoidosis or focal acral hyperkeratosis, knuckle pads, other forms of diffuse hyperkeratosis, the very rare "mosaic acral keratosis", and ainhum. A previous survey has shown that these various forms of PPK are particularly frequent in patients of Sub-Saharan African descent and that they commonly occur concurrently, suggesting that they could form part of a single entity called "African" Acral Keratoderma (AAK). AIM: To assess the validity of the concept of AAK and clarify its main characteristics. METHODS: A retrospective, descriptive, monocenter study was carried out on patients with AAK seen at our institution between 2009 and 2020. RESULTS: There were 42 patients (median age 38 years, range: 12-69 years), all of Sub-Saharan African descent. The male-female sex ratio was 0.3. Thirty-three (78%) had diffuse keratoderma, 25 (59%) had marginal keratoderma on their hands and/or feet, 20 (48%) had knuckle pads, 20 (48%) had keratosis punctata of the palmar creases, 3 had ainhum, and 2 had mosaic acral keratoderma. Mixed forms were seen in 76% of the patients (n = 32). Familial histories were reported by 17 patients (40%). Treatment was topical in over 90% of patients and systemic in 9 patients (21%). Ainhum was managed surgically. CONCLUSION: This retrospective study provides additional evidence for the concept of AAK. A genetic origin is suggested by the familial aggregation of cases.

Blaschko-linear lichen planus of the face: A retrospective study of 6 cases and a literature review.

INTRODUCTION AND METHODS: Different clinical and histological variants of lichen planus (LP) exist, such as lichen planopilaris, pigmentosus, linear, or atrophic LP. Recently, some cases came to our attention of hyperpigmented and atrophic linear lesions of the face with lichenoid histology, suggesting a combination of these different variants. We carried out a single-center, retrospective descriptive study of 6 similar cases selected from our database and compared them with a literature review. RESULTS: There were 4 males and 2 females of mean age 42 years. Each had linear lesions located on one side of the face. All lesions were initially itchy; they appeared hyperpigmented in all patients and atrophic in 5 cases. Biopsies indicated lichen planopilaris in 5 patients, with deep peri-eccrine involvement in 4 of them. Only 2 of the 6 patients had extra-facial lesions. DISCUSSION AND LITERATURE REVIEW: We found 24 cases in the literature having similar clinical and histological aspects. Men aged around 37 years seemed particularly affected. An atrophic course was noticed in 10 patients. Such a clinicopathological picture may suggest differential diagnoses like lichen striatus, lupus erythematosus, lichen sclerosus atrophicus, or Moulin's linear atrophoderma. Early histopathological examination could be of precious assistance in allowing the initiation of effective treatment immediately as of the initial inflammatory phase, thereby limiting the risk of cosmetic sequelae such as atrophy or residual pigmentation. CONCLUSION: We describe a form of facial lichen planus that is highly particular in terms of its follicular tropism, its blaschkoid distribution, its pigmented character, and its atrophic progression.

Male genital lichen planus: A retrospective study of 89 cases.

BACKGROUND: Unlike other types of lichen planus (LP), there are no series concerning male genital LP. OBJECTIVE: To describe the clinical characteristics, diagnosis, and response to treatment of male genital LP. PATIENTS AND METHODS: A retrospective study of male patients with genital LP consulting a dermatologist specialized in anogenital diseases between January 2010 and 2019. Demographic data, history, functional signs, clinical characteristics, pathology, complications, and treatment efficacy were collected. RESULTS: Eighty-nine patients were included at four centers. The median age was 51 years. Most patients were uncircumcised and asymptomatic. In 88.8% of cases, only the genital mucosa was involved. Erythema (71%), papules (21.3%), lacy network (15.7%), atrophic lesions (15.7%), erosions (14.6%), and post-inflammatory hyperpigmentation (2.2%) were less frequently observed. Biopsy results confirmed LP in 61.3% of cases but could not rule out other inflammatory genital dermatoses in other cases. Anatomic complications were observed in 30.3% of patients. Topical corticosteroids (TCS) induced remission in most cases. Tacrolimus efficacy was comparable to that of TCS. CONCLUSION: Male genital LP is a rare inflammatory disorder chiefly affecting uncircumcised men. It is found predominantly on the mucosal component of the penis and presents as non-erosive inflammatory balanitis in most cases, with frequent partial or complete remission on treatment with TCS.

Mycoplasma genitalium screening in a specialized French unit: A retrospective study.

OBJECTIVE: Mycoplasma genitalium (MG) infection accounts for 10-35% of non-gonococcal non-chlamydial (NGNC) urethritis. However, given that most people infected with MG do not develop symptoms and that antimicrobial resistance is increasing worldwide, there is no evidence of any benefits of screening asymptomatic individuals. We conducted this study to describe MG screening practices and outcomes at a French Sexually Transmitted Infections (STI) center in which MG testing was performed selectively and multiplex assays were not carried out [i.e., simultaneous screening for Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), and MG]. METHODS: A retrospective, observational, single-center study was conducted at the STI unit of Saint-Louis Hospital in Paris. The records of all patients undergoing MG testing from January 1st, 2017, to December 31st, 2018, were reviewed. The primary aim of the study was to describe and evaluate the proportion of MG-positive (MG+) patients among those tested. Secondary objectives were determination of the prevalence of MG+ status among symptomatic patients, risk factors associated with MG infection, and therapeutic modalities and efficacy. RESULTS: Two hundred and forty-nine patients underwent MG testing, 28 (11%) of whom were positive (MG+). The prevalence of MG+ status among symptomatic NGNC patients was 12%. HIV-positive (HIV+) status was significantly associated with MG+ status in univariate and multivariate analyses (Odds Ratio=7.3, 95% Confidence Interval 1.3-41.7; P=0.02). Twenty-three patients (85%) received antibiotics. Eighteen (67%) received azithromycin for 5 days, but 7 had clinical resistance. No quinolone resistance was reported. CONCLUSION: Despite unavailability of multiplex testing at our facility, which led to targeted-only screening for MG, its relatively high local prevalence is in keeping with what is generally observed at similar facilities across the world, where use of multiplex tests enables systematic screening for MG alongside NG and CT. This reinforces the current recommendations in Europe, France and the US against systematic MG testing or treatment in asymptomatic patients.

Image-guided lymph node core-needle biopsy predicts survival in mycosis fungoides and Sézary syndrome.

BACKGROUND: The prognosis of Sézary syndrome (SS) and mycosis fungoides (MF) depends on lymph node (LN) involvement. The usefulness of LN image-guided core-needle biopsies (CNBs), instead of surgical sampling, has been poorly evaluated. OBJECTIVES: To determine the prognostic value of LN CNB in MF/SS. METHODS: A retrospective search was conducted to identify all LN biopsy specimens of MF/SS between 2008 and 2019. Biopsies were staged according to the International Society for Cutaneous Lymphomas/European Organisation for Research and Treatment of Cancer (ISCL/EORTC) criteria. We performed immunolabelling and determined the tumour clone frequency (TCF) by high-throughput sequencing of the T-cell receptor beta locus. RESULTS: We included 119 consecutive biopsies from 100 patients, 45 with MF and 55 with SS. N1, N2 and N3 stages were diagnosed in 34 (29%), 26 (22%) and 59 (49%) cases, respectively. The TCF, Ki67 index, and percentage of cells positive for thymocyte selection-associated high mobility group box protein (TOX), programmed cell death protein 1 (PD1), killer cell immunoglobulin-like receptor 3DL2 (KIR3DL2) and cluster of differentiation (CD)30 were all positively correlated with the N stage. Median overall survival (OS) for N1/N2 vs. N3 patients was 42 months (range 26-not reached) vs. 14 months (range 5-30), respectively (P < 0·001). In univariate analyses, an age > 75 years, LN short-axis diameter > 15 mm, N3 stage, presence of large-cell transformation, TOX > 60%, PD1 > 25%, Ki67 > 30%, KIR3DL2 > 15%, CD30 > 10% and TCF > 25% were identified as adverse prognostic factors. In multivariate analyses, only an age > 75 years and Ki67 index > 30% were associated with reduced OS. We developed a new prognostic index associating the N stage and the Ki67 index, which better discriminates N3 patients with poor prognosis. CONCLUSIONS: CNB allows an objective assessment of the LN involvement in MF/SS, relevant for staging and prognosis.

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.

Multicentric EORTC retrospective study shows efficacy of brentuximab vedotin in patients who have mycosis fungoides and Sézary syndrome with variable CD30 positivity.

BACKGROUND: Brentuximab vedotin (BV) was approved as a therapy for mycosis fungoides (MF) based on the ALCANZA trial. Little real-world data, however, are available. OBJECTIVES: To evaluate the efficacy and safety of BV in patients with MF/Sézary Syndrome (SS) with variable CD30 positivity in a real-world cohort and to explore potential predictors of response. METHODS: Data from 72 patients with MF/SS across nine EORTC (European Organization for Research and Treatment of Cancer) centres were included. The primary endpoint was to evaluate the proportion of patients with: overall response (ORR), ORR lasting over 4 months (ORR4), time to response (TTR), response duration (RD), progression-free survival (PFS) and time to next treatment (TTNT). Secondary aims included a safety evaluation and the association of clinicopathological features with ORR, RD and TTNT. RESULTS: All 72 patients had received at least one systemic treatment. ORR was achieved in 45 of 67; ORR4 in 28 of 67 with a median TTR of 8 weeks [interquartile range (IQR) 5·5-14] and with a median RD of 9 months (IQR 3·4-14). Median PFS was 7 months (IQR 2-12) and median TTNT was 30 days (6-157·5). Patient response, RD, PFS and TTNT were not associated with any clinicopathological characteristics. In the MF group, patients with stage IIB/III vs. IV achieved longer PFS and had a higher percentage of ORR4. There was a statistically significant association between large-cell transformation and skin ORR (P = 0·03). ORR4 was more frequently achieved in patients without lymph node involvement (P = 0·04). CONCLUSIONS: BV is an effective option for patients with MF/SS, including those with variable CD30 positivity, large-cell transformation, SS, longer disease duration and who have been treated previously with several therapies.