Nailfold dermoscopy predicts the absence of a capillaroscopy sclerodermic pattern: The multicentre, prospective VASCUL-R trial.

BACKGROUND: Nailfold capillaroscopy is recommended to diagnose primary or secondary Raynaud's phenomenon (RP). Capillaroscopy is normal in primary RP, which is the most frequent. Screening for RP capillary anomalies with nailfold dermoscopy has been promising. OBJECTIVE: To determine whether normal nailfold dermoscopy-based on the absence of five criteria that define a sclerodermic pattern-is able to predict normal capillaroscopy with good positive-predictive value (PPV). METHODS: Prospective, 2-phase (monocentre and multicentre) study on patients at first consultation for RP undergoing nailfold video capillaroscopy (NVC) and nailfold dermoscopy by two different 'blinded' trained observers, respectively, a vascular specialist and a dermatologist, not familiar with capillaroscopy. The five criteria noted were as follows: disorganization, megacapillaries, low capillary density, avascular areas and haemorrhages. RESULTS: Based on 105 patients, the dermoscopy PPV for a normal NVC was 100% (p = 0.015), with 37.9% sensitivity, when no criterion was observed. Excluding haemorrhages, the PPV remained 100% (p < 0.0001), with sensitivity rising to 73.7% and 100% specificity. CONCLUSION: Normal nailfold dermoscopy with the absence of four easy-to-observe criteria predicts normal NVC with an excellent PPV.

Aetiological treatment of venous leg ulcers with compression therapy: real-life outcomes with two different procedures.

OBJECTIVE: To evaluate the healing outcomes and costs associated with the aetiological management of venous leg ulcers (VLUs) treated with recommended multicomponent bandages (MCBs) and short-stretch bandages (SSBs). METHOD: This observational study is a retrospective comparative study (Level 2b), based on the French administrative healthcare database (Système National des Données de Santé, SNDS). It includes patients treated from onset with reimbursed MCBs and SSBs for a VLU episode, between July 2018 and September 2020. Although other compression systems, such as long-stretch bandages, are commonly used for the treatment of VLUs, they are not recommended by health authorities in France and thus, were not considered for this study. A binomial regression model was performed to estimate the adjusted relative risk of wound closure rates at three months for each group, based on potential confounding factors including, notably, age, sex, key comorbidities, and wound dressing size. The mean healthcare cost was calculated for patients whose VLUs healed within the study period. RESULTS: The reimbursement data (including prescribed compression systems and nursing care) of the 25,255 selected patients were analysed in the study. There were no significant differences between the MCBs and SSBs groups when considering patient characteristics. The healing rates after three months' treatment, were 42% and 35% (p<0.001) in the MCBs and SSBs groups, respectively. When adjusting the statistical model, the chance of healing at three months was still 12% higher with MCBs compared with SSBs (p<0.0001). The median healing time was estimated at 115 (interquartile range (IQR): 60-253) days in the MCB group versus 137 (IQR: 68-300) days in the SSBs group. The average treatment cost per patient with a healed ulcer was €2875±3647 in the MCB group and €3580±5575) in the SSBs group (p=0.0179), due to lower hospital stay and nursing costs in the MCB group. Differences in wound characteristics between the two groups cannot be totally excluded, due to the limited content of the database in terms of clinical data, but should have been addressed, to some extent, through the study selection criteria and the chosen regression model. CONCLUSION: In this study, this SNDS analysis seemed to confirm that the healing outcomes achieved in real-life with MCBs were in line with those reported in clinical trials, and superior to SSBs, which reinforces the current position from the guidelines.

Elastic fiber alterations and calcifications in calcific uremic arteriolopathy.

Calcific uremic arteriolopathy (CUA) is a severely morbid disease, affecting mostly dialyzed end-stage renal disease (ESRD) patients, associated with calcium deposits in the skin. Calcifications have been identified in ESRD patients without CUA, indicating that their presence is not specific to the disease. The objective of this retrospective multicenter study was to compare elastic fiber structure and skin calcifications in ESRD patients with CUA to those without CUA using innovative structural techniques. Fourteen ESRD patients with CUA were compared to 12 ESRD patients without CUA. Analyses of elastic fiber structure and skin calcifications using multiphoton microscopy followed by machine-learning analysis and field-emission scanning electron microscopy coupled with energy dispersive X-ray were performed. Elastic fibers specifically appeared fragmented in CUA. Quantitative analyses of multiphoton images showed that they were significantly straighter in ESRD patients with CUA than without CUA. Interstitial and vascular calcifications were observed in both groups of ESRD patients, but vascular calcifications specifically appeared massive and circumferential in CUA. Unlike interstitial calcifications, massive circumferential vascular calcifications and elastic fibers straightening appeared specific to CUA. The origins of such specific elastic fiber's alteration are still to be explored and may involve relationships with ischemic vascular or inflammatory processes.

Severe Scabies: A French Multi-centre Study Involving 95 Patients with Crusted and Profuse Disease and Review of the Literature.

The aim of this multi-centre French retrospective study was to identify severe, i.e. crusted and profuse, scabies patients. Records were retrieved from 22 Dermatology or Infectious Diseases departments in the Ile-de-France from January 2009 to January 2015 to characterize epidemiology, demography, diagnosis, contributing factors, treatment features, and outcomes in severe scabies. A total of 95 inpatients (57 crusted and 38 profuse) were included. A higher number of cases was observed among elderly patients (>75 years), mostly living in institutions. Thirteen patients (13.6%) reported a history of previously treated scabies. Sixty-three patients (66.3%) had been seen by a previous practitioner for the current episode (up to 8 previous visits). Initial misdiagnosis (e.g. eczema, prurigo, drug-related eruptions, psoriasis) was documented in 41 patients (43.1%). Fifty-eight patients (61%) had already received 1 or more previous treatments for their current episode. Forty percent received corticosteroids or acitretin for an initial diagnosis of eczema or psoriasis. Median time from the onset of symptoms to the diagnosis of severe scabies was 3 months (range 0.3-22). Itch was present in all patients at diagnosis. Most patients (n=84, 88.4%) had comorbidities. Diagnostic and therapeutic approaches varied. Complications occurred in 11.5% of cases. To date, there is no consensus for diagnosis and treatment, and future standardization of is required for optimal management.

Efficacy and Safety of Botulinum Toxin in Adults with Raynaud's Phenomenon Secondary to Systemic Sclerosis: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study.

OBJECTIVE: To determine whether a single session of botulinum toxin type A (BTA) injections into both hands more effectively decreases the frequency of systemic sclerosis-associated Raynaud's phenomenon (SSc-RP) episodes than placebo. METHODS: This multicenter, randomized, double-blind, placebo-controlled, parallel-group phase III trial in patients with SSc-RP assessed the effect of 50-unit BTA or placebo injections into the palms of both hands around each neurovascular bundle during 1 session in winter. The primary end point was the between-group difference in the median change in the number of RP episodes from baseline (day 0) to 4 weeks postinjection. Values between the groups were compared with the Wilcoxon rank-sum test. RESULTS: The intent-to-treat analysis included 46 BTA-treated patients and 44 placebo recipients. At 4 weeks after assigned treatment injections, the median number of daily RP episodes decreased comparably in the BTA and placebo groups (median change -1 episode/day [interquartile range (IQR) -1.5, 0 episodes/day] and -1 episode/day [IQR -2.5, 0 episodes/day], respectively) (P = 0.77 versus placebo). Moreover, change in Raynaud's Condition Score, quality of life assessed by Health Assessment Questionnaire disability index, and hand function assessed by shortened Disabilities of the Arm, Shoulder, and Hand (QuickDASH) and Cochin Hand Function Scale from baseline to follow-up weeks 4, 12, and 24 did not differ significantly between groups. The BTA group experienced transient hand muscle weakness significantly more frequently (P = 0.003). CONCLUSION: Neither the primary nor secondary end points were reached, and our results do not support any beneficial effect of palmar BTA injections to treat SSc-RP.

A new compression system for treatment of venous leg ulcers: a prospective, single-arm, clinical trial (FREEDOM).

OBJECTIVE: To evaluate the efficacy, tolerability and acceptability of a new multicomponent compression system in one bandage for the local treatment of patients with venous leg ulcers (VLUs). METHOD: This was an international, prospective, non-comparative, clinical trial, conducted in France and Germany. Eligible participants had a VLU with a wound area of 2-20cm2, lasting for a maximum of 24 months. For a period of 6 weeks, patients were treated with a new multicomponent compression system in one bandage which was worn day and night, providing high working pressure and moderate resting pressure (UrgoK1). Clinical assessments, wound measurement and photographs were planned at weeks 1, 2, 4 and 6. The primary endpoint was the relative wound area reduction (RWAR) after 6 weeks of treatment. Secondary endpoints included wound closure rate, oedema resolution, change in patient's health-related quality of life (HRQoL), acceptability, adherence to the compression therapy, local tolerance, and physician's overall satisfaction with the evaluated compression system. RESULTS: A cohort of 52 patients (52% female, mean age 75.4±13.0 years) with VLUs, including oedema in 58% of cases, were recruited from 22 centres. At baseline, 42 patients had already been treated with a different compression system. VLUs had been present for 5.6±4.9 months and had a mean area of 5.7±4.3cm2. After 6 weeks of treatment, a median RWAR of 91% (interquartile range: 39.4; 100.0) was achieved. Wound closure was reported in 35% of patients. A RWAR ≥40% at week 4, predictive of wound healing at 12 weeks, was achieved in 62% of patients. At the final visit, oedema present at baseline was resolved in 57% of patients. Substantial improvements in the HRQoL of the patients were reported with a decrease of the pain/discomfort and anxiety/depression dimensions. Comfort in wearing the evaluated system was reported as 'very good' or 'good' by 79% of patients, resulting in a high patient adherence to compression therapy. Compared to previous compression systems, half of the patients reported more ease in wearing shoes, and greater satisfaction and comfort with this new system. Nine non-serious adverse events related to the device or its procedure occurred in seven patients. At the final visit, the majority of the physicians were 'very satisfied' or 'satisfied' with the new compression system overall. CONCLUSION: The new multicomponent compression system in one bandage has been shown to promote rapid healing of VLUs, reduce oedema, improve HRQoL and to be well tolerated and accepted. It appears to be a viable alternative to existing compression systems.

Correlation of nailfold capillaroscopy findings with history of digital ulcer on same finger: Results of SCLEROCAP study.

Systemic sclerosis may be complicated by digital ulcers. Nailfold capillaroscopy on one finger might reflect an increased risk of digital ulcer (DU). In the present study we studied the correlations between a history of ulcer and capillary findings on the finger. METHOD: This study is part of Sclerocap, a multicenter study aiming at validating prospectively the prognostic value of Maricq's and Cutolo's capillaroscopic classifications during a three-year longitudinal follow-up. A history of past or present digital ulcer was recorded at inclusion and nailfold capillaroscopy was performed. Elementary findings as well as Cutolo and Maricq's classifications were assessed. RESULTS: 387 patients were included in Sclerocap (327 females, 60 males) and 3096 fingers were examined by capillaroscopy at inclusion: 316 fingers (10%) belonging to 113 patients had a history of DU. Late Cutolo's stage was statistically correlated with a history of DU, both by univariate: OR 2.08 [1.09-3.96] and multivariate analysis: OR 1.97 [1.06-3.63]. Among the elemental abnormalities, only edema and decreased capillary density were correlated with a history of DU by multivariate analysis: respectively OR 1.92 [1.17-3.16] and 0.65 [0.49-0.85]. CONCLUSION: This cross-sectional study in a large cohort of patients with systemic sclerosis shows a correlation between a history of digital ulcer and edema, a decrease in capillary density and the late stage in Cutolo's classification. The extent of capillary abnormalities on one finger is associated with a history of local digital ulcer. Capillaroscopy might be used to predict the risk of DU but these results need first to be confirmed by prospective studies.

Prevalence and factors associated with long-term remission in cutaneous lupus: A longitudinal cohort study of 141 cases.

BACKGROUND: Little is known about the prevalence and factors associated with long-term remission in cutaneous lupus erythematosus (CLE). OBJECTIVES: To assess the prevalence, the factors associated with remission, and the long-term remission with and without treatment during CLE. METHODS: Longitudinal cohort study including biopsy-proven patients with CLE seen between November 1, 2019 and April 30, 2021, with at least 6 months of follow-up after diagnosis. Demographic data, CLE subtypes, remission status, and treatments were recorded. Remission was defined by a Cutaneous Lupus Erythematosus Disease Area and Severity Index activity score of 0. Long-term remission was defined by remission >3 years. RESULTS: Among 141 patients included (81% of women), 93 (66%) were in remission at last follow-up with a median duration since diagnosis of 11.4 years (interquartile range, 4.2-24.7). Long-term remission was observed in 22 (19%) of 114 patients with at least 3 years of follow-up, including 5 (4.4%) with no systemic treatment. Active smoking (odds ratio, 0.22 [95%CI: 0.05-0.97]; P = .04) and discoid CLE lesions (odds ratio, 0.14 [95%CI, 0.04-0.48]; P = .004) were associated with a lower risk of long-term remission. LIMITATIONS: Partial retrospective data collection and tertiary center population. CONCLUSION: Long-term remission is rare in CLE and negatively associated with active smoking and discoid CLE.

Finger Systolic Blood Pressure Index Measurement: A Useful Tool for the Evaluation of Arterial Disease in Patients With Systemic Sclerosis.

OBJECTIVE: To evaluate the prevalence and clinical correlates of peripheral arterial disease of the upper limbs in patients with systemic sclerosis (SSc), as detected with finger brachial pressure index (FBPI) measurements. METHODS: This work is based on the baseline data of the SCLEROCAP multicenter cohort of SSc patients. Finger systolic blood pressure was measured with laser Doppler flowmetry, and the FBPI was obtained as its ratio over the ipsilateral brachial systolic blood pressure. An FBPI of <0.70 was used as the diagnostic criterion for occlusive arterial disease of the upper limbs. Thus, the prevalence of defined arterial disease as well as its clinical, biologic, and capillaroscopic correlates were evaluated. RESULTS: Among 326 enrolled patients, 177 (54.3%) met the criterion for arterial disease (FBPI <0.70). No association was found with the type of SSc nor with the type of associated antinuclear antibodies, but a significant association was found with the duration of the disease (P < 0.001), the capillaroscopic pattern (P < 0.001), and most strikingly with the presence of digital ulcers (42.9% versus 13.4%; P < 0.001). A quantitative relationship was found between the FBPI and the prevalence of digital ulcers and was shown to be independent from the capillaroscopic pattern. CONCLUSION: This cross-sectional study shows a high prevalence of arterial disease of the upper limbs in patients with SSc. FBPI appears to be a strong and independent predictor of digital ulcers. This study suggests that both macro- and microangiopathy are contributing to the ischemic damage of the fingertips.

Myeloid Clonal Infiltrate Identified With Next-Generation Sequencing in Skin Lesions Associated With Myelodysplastic Syndromes and Chronic Myelomonocytic Leukemia: A Case Series.

Background: Myelodysplastic syndromes (MDS) and chronic myelomonocytic leukemia (CMML) are associated with cutaneous manifestations. Next-generation sequencing (NGS) is a tool capable of identifying clonal myeloid cells in the skin infiltrate and thus better characterize the link between hematological diseases and skin lesions. Objective: To assess whether skin lesions of MDS/CMML are clonally related to blood or bone marrow cells using NGS. Methods: Comparisons of blood or bone marrow and skin samples NGS findings from patients presenting with MDS/CMML and skin lesions in three French hospitals. Results: Among the 14 patients recruited, 12 patients (86%) had mutations in the skin lesions biopsied, 12 patients (86%) had a globally similar mutational profile between blood/bone marrow and skin, and 10 patients (71%) had mutations with a high variant allele frequency (>10%) found in the myeloid skin infiltrate. Mutations in TET2 and DNMT3A, both in four patients, were the most frequent. Two patients harbored a UBA1 mutation on hematopoietic samples. Limitations: Limited number of patients and retrospective collection of the data. Blood and skin sampling were not performed at the exact same time point for two patients. Conclusion: Skin lesions in the setting of MDS/CMML are characterized by a clonal myeloid infiltrate in most cases.

Nailfold capillaroscopy findings in cutaneous lupus erythematosus patients with or without digital lesions and comparison with dermatomyositis patients: A prospective study.

BACKGROUND: Differential diagnosis between cutaneous lupus erythematosus (CLE) and dermatomyositis (DM) may be challenging if digital lesions occur. OBJECTIVES: To compare nailfold capillaroscopy (NFC) findings in CLE patients with or without digital involvement, and to compare capillaroscopic findings between CLE patients with digital lesions and DM patients. METHODS: Prospective monocentric study including CLE and DM patients. NFC was performed and standardized items were recorded. RESULTS: Fifty-one CLE patients and 10 DM patients with digital lesions were included. A scleroderma pattern was found in 6 patients (12%): in 5 out of 17 patients with digital lesions, compared with only 1 out of 34 patients without digital lesions (p = 0.01). In multivariate analysis, CLE digital lesions and digital ulcerations were statistically associated with scleroderma pattern. CLE digital lesions were significantly associated with architectural disorganization (p = 0.0003) and capillary rarefaction (p = 0.0038). A scleroderma pattern was significantly more frequent in DM patients (80%) than in CLE patients with digital lesions (30%, p = 0.018). Capillaroscopic findings were not significantly different between CLE patients with digital lesions and DM patients. CONCLUSION: Although scleroderma pattern is more frequent in DM patients than in CLE patients with digital lesions, NFC cannot formally distinguish CLE from DM.

Systemic sclerosis is associated with lower limb vascular stiffness and microvascular impairment: results from a prospective study.

OBJECTIVE: Systemic sclerosis (SSc) is a connective tissue disease characterized by microangiopathy. Peripheral arterial disease, increasingly studied during SSc, is responsible for digital ulcers, associated with a high risk of amputation. The aim of our study was to assess the frequency of lower limb arterial impairment in SSc patients by measuring ankle-brachial index (ABI), toe pressure (TP), and toe-brachial index (TBI). METHODS: Systemic sclerosis patients were included prospectively during 1 year in Tenon and Saint-Antoine Hospitals, Paris. Clinical and biological data were recorded. For each patient, ABI, TP, and TBI were measured and an arterial duplex ultrasonography was prescribed in case of abnormal results. RESULTS: Eighty-six patients were included (94% women, median age 62 years). Only 24% of them had no lower limb hemodynamic vascular abnormalities; 44% had an isolated microvascular abnormality (normal ABI and TBI<0.75); 31% had at least a macrovascular injury associated or not with microvascular impairment (abnormal ABI) and 12.6% had a TP<50 mmHg. During follow-up, there was a trend towards association of low TBI with more major adverse event (all-cause mortality, non-fatal stroke, non-fatal myocardial infarction, and lower limb ischemic manifestations) than normal TBI. CONCLUSION: By measuring ABI and TP, we showed that 76% of SSc patients had hemodynamic arterial lower limb abnormalities related to macro- and/or microvascular impairment and that 28% had vascular stiffness. In SSc patients, ABI is not an accurate tool to detect lower limb arterial disease, likely due to underlying micro- and macrovascular changes. Key Points • The presence of lower limb macro-and/or microvascular involvement was detected in 76% of SSc patients. • In SSc patients, ABI is not an accurate tool to detect lower limb arterial disease, likely due to underlying microvascular changes and frequent arterial stiffness.