Search

Khaled Ezzedine, 1 Anne Claire Fougerousse, 2, 3 Roberte Aubert, 4 Jean-Benoît Monfort, 5 Ziad Reguiaï, 3, 6 Jason Shourick, 7 Charles Taieb, 8, 9,* François Maccari 3, 10,* 1Private Pratice, La Varenne Saint Hilaire, France; 2Hôpital d’instruction des armées, Saint-Mandé, France; 3Resopso, Paris, France; 4France Psoriasis, Association de Patients, Paris, France; 5Hôpital Cochin, Paris, France; 6Service de Dermatologie, Polyclinique Courlancy-Bezannes, Reims, France; 7Université Paris Sud, Paris, France; 8Santé Publique, Hôpital Necker Enfants Malades, Paris, France; 9European Market Maintenance Assessment, Fontenay-sous-Bois, France; 10EA EpiDermE UPEC-Université Paris-Est Créteil, Creteil, France*These authors contributed equally to this workCorrespondence: Charles Taieb Tel +33 771 772 100Email charles.taieb@emma.clinicBackground: Psoriasis impacts independently of its severity on patients’ lifestyle and quality of life (QoL).Aim: To build a tool for assessing the patient-reported psoriasis burden.Methods: An expert group created a questionnaire using a standardized methodology building questionnaires assessing quality of life issues. The questionnaire was translated from French into a cultural and linguistically validated US English version.Results: A conceptual questionnaire of 54 questions was created. The confirmatory analyses resulted in a 10-feature questionnaire divided into 4 internally consistent domains with a Cronbach’s alpha coefficient of 0.9. It was reproducible and highly reliable. It correlated well with the Dermatology Life Quality Index (DLQI), Perceived Stress Scale (PSS), and SF-12 mental and SF12 physical scores.Conclusion: This tool allows for the first time to assess the burden of psoriasis patients. Its use may allow improving medical and nonmedical patient care, thus improving their daily life.Keywords: disease burden, psoriasis, quality of life, questionnaire, standardized method

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., (© 2024 European Academy of Dermatology and Venereology.)

Familial Mediterranean fever is the most common monogenic auto-inflammatory disease in the world. It mainly affects people originating from the Mediterranean region. The mutated gene is MEFV, which codes for pyrin. Transmission is autosomal recessive. Patients present with recurrent attacks of fever since childhood associated with abdominal and/or thoracic pain lasting an average of 2-3days and a biological inflammatory syndrome. Other symptoms include arthralgia or arthritis in large joints such as the knees and ankles, myalgia in the lower limbs and pseudo-erysipelas in the ankles. The most serious complication is inflammatory amyloidosis, which can lead to kidney failure. Treatment is based on colchicine, which helps to prevent flares and the onset of renal amyloidosis. This paper proposes national guidelines for the diagnosis, management and follow-up of familial Mediterranean fever in France, where we estimate there are between 5000 and 10,000 patients with the disease at all stages of life. The diagnosis is suspected on the basis of clinical and anamnestic factors and confirmed by genetic analysis. These guidelines also suggest a "treat-to-target" approach to disease management, particularly in case of suspected colchicine resistance - a very rare situation that should remain a diagnosis of elimination, especially after colchicine compliance has been verified. Two special situations are also addressed in these guidelines: kidney failure and pregnancy., (Copyright © 2023. Published by Elsevier Masson SAS.)

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., (© 2023. Springer Nature Limited.)

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., (© 2022 American College of Rheumatology.)

Competing Interests: Conflicts of interest None disclosed.

Objective: The frequency of vasculitis may be increased in patients with Familial Mediterranean Fever (FMF), according to several studies. Our aim was to assess the characteristics of French adult patients with both diseases., Methods: Patients with vasculitis were selected from patients followed for FMF in the French JIR-cohort., Results: Twenty-two patients were included [polyarteritis nodosa (PAN) n = 10, IgA vasculitis n = 8, unclassified vasculitis n = 2, granulomatosis with polyangiitis n = 1, and microscopic polyangiitis n = 1]. Pathogenic mutations in exon 10 were found in all 21 patients (96%) for which MEFV testing results were available, and 18 (82%) had two pathogenic mutations. Histology showed vasculitis in 59% of patients. Most patients with FMF-associated PAN were HBV-negative and had an inactive FMF before PAN onset, and 40% had a peri-renal or central nervous system bleeding. Most patients with FMF-associated IgA vasculitis had an active FMF before vasculitis onset, and 25% had digestive bleeding. Both patients with unclassified vasculitis had ischemic and/or hemorrhagic complications., Conclusion: This study confirms the predominance of PAN and IgA vasculitis in patients with FMF and the high frequency of bleeding in FMF-associated PAN. FMF should be considered in case of persistent symptoms and/or inflammatory syndrome despite vasculitis treatment in Mediterranean patients., Competing Interests: SG-L and GG received honoraria as speakers or occasional consultants for the SOBI and Novartis laboratories (5000 euros). The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Abbara, Monfort, Savey, Moguelet, Saadoun, Bachmeyer, Fain, Terrier, Amoura, Mathian, Gilardin, Buob, Job-Deslandre, Dufour, Sberro-Soussan, Grateau and Georgin-Lavialle.)

Competing Interests: Conflict of interest None disclosed.

Background: Leg ulcers in adults are a major public health concern. Their incidence increases with age and many causes have been identified, predominantly associated with vascular diseases. Leg ulcers in children and teenagers are less frequent. The aim of our study was to identify the causes of leg ulcers in children and teenagers, and to evaluate their management., Methods: This retrospective multicenter study was conducted by members of the Angio-dermatology Group of the French Society of Dermatology and of the French Society of Pediatric Dermatology. Data from children and teenagers (< 18 years), seen between 2008 and 2020 in 12 French hospitals for chronic leg ulcer (disease course>4 weeks), were included., Results: We included 27 patients, aged from 2.3 to 17.0 years. The most frequent causes of leg ulcer were: general diseases (n=9: pyoderma gangrenosum, dermatomyositis, interferonopathy, sickle cell disease, prolidase deficiency, scleroderma, Ehlers-Danlos syndrome), vasculopathies (n=8: hemangioma, capillary malformation, arteriovenous malformation), trauma (n=4: bedsores, pressure ulcers under plaster cast), infectious diseases (n=4: pyoderma, tuberculosis, Buruli ulcer) and neuropathies (n=2). Comorbidities (59.3%) and chronic treatments (18.5%) identified as risk factors for delayed healing were frequent. The average time to healing was 9.1 months., Discussion: Leg ulcers are less frequent in children and teenagers than in adults and their causes differ from those in adults. Comorbidities associated with delayed healing must be identified and managed. Children and teenagers tend to heal faster than adults, but a multidisciplinary management approach is necessary., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

Cutaneous drug-induced lupus erythematosus (CDILE) is a lupus-like syndrome related to drug exposure which typically resolves after drug discontinuation. It can present as a systemic or a sole cutaneous form and different drugs may be associated with each form. CDILE pharmacoepidemiology is constantly changing. Indeed, older drugs primarily associated with systemic CDILE are no longer prescribed and new drugs associated with either cutaneous or systemic CDILE have emerged. The present study discusses the clinical and laboratory aspects of CDILE and the postulated pathogenesis, and it provides an update on implicated drugs. We performed a literature review to single out the new drugs associated with CDILE in the past decade (January 2010-June 2020). Among 109 drugs reported to induce CDILE in 472 patients, we identified anti-TNFα, proton-pump inhibitors, antineoplastic drugs, and, in particular, checkpoint inhibitors, as emerging drugs in CDILE. Most of the published studies are cases reports or small case series, and further larger studies as well as the development of validated classification criteria are needed to better understand and characterize their implication in CDILE., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

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., (© 2021. International League of Associations for Rheumatology (ILAR).)

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.

Competing Interests: Conflict of interest None disclosed.

Background: Acral lesions, mainly chilblains, are the most frequently reported cutaneous lesions associated with COVID-19. In more than 80% of patients tested, nasopharyngeal swabs were negative on reverse transcription polymerase chain reaction (RT-PCR) for SARS-CoV-2 when performed, and serology was generally not performed., Methods: A national survey was launched on 30 March 2020 by the French Society of Dermatology asking physicians to report cases of skin manifestations in patients with suspected or confirmed COVID-19 by using a standardized questionnaire. We report the results for acral manifestations., Results: We collected 311 cases of acral manifestations [58.5% women, median age 25.7 years (range 18-39)]. The most frequent clinical presentation (65%) was typical chilblains. In total, 93 cases (30%) showed clinical suspicion of COVID-19, 67 (22%) had only less specific infectious symptoms and 151 (49%) had no clinical signs preceding or during the course of acral lesions. Histology of skin biopsies was consistent with chilblains. Overall, 12 patients showed significant immunological abnormalities. Of the 150 (48%) patients who were tested, 10 patients were positive. Seven of 121 (6%) RT-PCR-tested patients were positive for SARS-CoV-2, and five of 75 (7%) serology-tested patients had IgG anti-SARS-CoV-2. Tested/untested patients or those with/without confirmed COVID-19 did not differ in age, sex, history or acral lesion clinical characteristics., Conclusions: The results of this survey do not rule out that SARS-CoV-2 could be directly responsible for some cases of chilblains, but we found no evidence of SARS-CoV-2 infection in the large majority of patients with acral lesions during the COVID-19 lockdown period in France. What is already known about this topic? About 1000 cases of acral lesions, mainly chilblains, were reported during the COVID-19 outbreak. Chilblains were reported to occur in young people within 2 weeks of infectious signs, which were mild when present. Most cases did not have COVID-19 confirmed by reverse transcription polymerase chain reaction (RT-PCR), and few serology results were available. What does this study add? Among 311 patients with acral lesions, mainly chilblains, during the COVID-19 lockdown period in France, the majority of patients tested had no evidence of SARS-CoV-2 infection. Overall, 70 of 75 patients were seronegative for SARS-Cov-2 serology and 114 of 121 patients were negative for SARS-CoV-2 RT-PCR., (© 2020 British Association of Dermatologists.)

Introduction: This is a clinical case illustrating a diagnosis of an IgG4 related-disease (IgG4-RD) diagnosed in a vascular context., Case Report: A 47-year-old man with no past medical history consulted for a recent and disabling Raynaud phenomenon without trophic disorder. Vascular examinations revealed multiple arterial thromboses with no abnormal finger and toe pressures. Secondly, weight loss and submandibular glands enlargement appeared, leading to the diagnosis of IgG4-RD without a link being able to be established with vascular involvement. This is the second observation of this association. A French translation of the new classification criteria for IgG4-RD published in 2019 by the American College of Rheumatology and European Ligue Against Rhumatism (ACR/EULAR) is offered with direct application to the clinical case., Conclusion: A Raynaud phenomenon with distal arterial thrombosis is rarely observed in the IgG4-RD., (Copyright © 2020. Published by Elsevier Masson SAS.)

Objectives: Mucosal-associated invariant T (MAIT) cells are innate-like lymphocytes that are important for antibacterial immunity and may have regulatory roles. MAIT cells are decreased during SLE. However, their frequencies and phenotype have not been investigated in DM. We studied MAIT cell frequencies and phenotype in DM patients with active and inactive disease (after treatment)., Methods: Peripheral blood flow cytometry analysis of MAIT cells was compared between DM (n = 22), SLE (n = 10), psoriasis (n = 7) and atopic dermatitis (n = 5) patients, and healthy controls (n = 19)., Results: A dramatic decrease of circulating MAIT cell frequency was observed in active DM and SLE patients compared with healthy controls and other inflammatory skin diseases [active DM: median = 0.25% (interquartile range 0.19-0.6%), P < 0.0001; active SLE: median = 0.61 (0.55-0.77), P < 0.0001 vs healthy controls: 2.32% (1.18-4.45%)]. MAIT cells from active DM patients had an abnormal phenotype including increased expression of CD25 and cytotoxic T-lymphocyte-associated protein 4 that correlated with their low frequency in the blood., Conclusion: In DM, peripheral blood MAIT cells are dramatically reduced and have an activated/exhausted phenotype that may be linked to increased activation-induced cell death., (© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Significance: Sickle-cell leg ulcers (SCLUs) are a severe, chronic, and recurrent complication of sickle-cell disease (SCD). There are no official recommendations for treatment. Recent Advances: Only a few studies with a high level of evidence have been conducted to evaluate treatment of SCLUs. However, several studies have been conducted with a high level of evidence to evaluate the efficacy of treatments in venous leg ulcers, and SCLUs could benefit from these treatments, especially when a venous incompetence or an edema is associated. Pathophysiology of SCLUs includes a vasculopathy related to chronic hemolysis and an endothelial dysfunction, which could be therapeutic approaches to SCLU treatment. Critical Issues: Therapeutic approaches to SCLUs can target SCD on the one hand and skin healing and associated aggravating factors on the other. A review of the literature found only case series and six randomized controlled trials; some offered encouraging results, but most had serious biases. Clinical trials specifically targeting SCLUs are difficult to realize because of the small number of affected patients, in comparison with patients with leg ulcers from other causes. Future Direction: Treating SCLUs remains a challenge. Data in the literature are currently insufficient to offer clear treatment guidelines because of several biases in controlled studies. New studies are under way to assess the efficacy of topical treatments and describe the microbiome of SCLUs. Prevention of SCLU recurrence should be assessed in future clinical trials because the high risk of recurrence is an unsolved critical issue.

Background: We have limited data on the treatment of calcinosis cutis associated with systemic sclerosis and dermatomyositis., Objective: To assess the efficacy and tolerance of available treatments for calcinosis cutis based on previously published studies., Methods: We performed a systematic review of studies published in Medline, Embase, and the Cochrane library during 1980-July 2018. The strength of clinical data was graded according to the modified Oxford Centre for Evidence-Based Medicine levels of evidence., Results: In all, 30 studies (288 patients) were included. Eleven therapeutic classes, surgery, and physical treatments were identified as potential treatment options for calcinosis cutis. On the basis of results of a small randomized controlled trial and 4 retrospective studies, low-dose warfarin should not be used for calcinosis cutis (level IB evidence). The results of several studies suggest diltiazem and bisphosphonates might be useful treatment options (level IV). Considering biologic therapies, rituximab has shown promising results in treating both dermatomyositis and systemic sclerosis, whereas tumor necrosis factor inhibitors might be useful for treating juvenile dermatomyositis (level IV). Intralesional sodium thiosulfate might be a promising alternative (level IV)., Limitations: Few included studies had a high level of evidence., Conclusion: This study highlights the efficacy and tolerance profiles of available treatments for calcinosis cutis, with a focus on level of evidence., (Copyright © 2019 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Chilblains are inflammatory dermal lesions associated with hypersensitivity to cold, and they occur on the extremities bilaterally and symmetrically. Their onset during the course of pro-thermogenic and autoimmune diseases has been widely reported, but the association with predisposing locoregional causes is not well known., Patients and Methods: Case 1: a 57-year-old man, who smoked 80 packets per year, presenting a deficit of the levator muscles in his right foot following lumbar sciatica with paralysis of L5, consulted for unilateral necrotic lesions of the toes recurring each winter in the paralysed limb only. Case 2: a 60-year-old man had a previous history of liposarcoma of the right side treated with radiotherapy and surgery, resulting in sequelae of monoparesis and radiation-induced arteritis. Each winter, he presented recurring unilateral purpuric macules of the toes on his right foot, with no necrotic progression. In both cases, clinical examination, disease progression over time, histology and laboratory tests confirmed the diagnosis of idiopathic chilblains., Conclusion: The physiopathological hypotheses posited to account for the unilateral appearance of chilblains in the event of paralysis include decreased blood flow to the paralysed limb, imbalance in neuromodulators, dysfunction of the autonomous nervous system, cutaneous atrophy with hypertrophy of underlying soft tissues, and finally, hypoesthesia aggravating the trophic disorders., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Importance: Calcific uremic arteriolopathy (CUA), a rare, potentially fatal, disease with calcium deposits in skin, mostly affects patients with end-stage renal disease who are receiving dialysis. Chemical composition and structure of CUA calcifications have been poorly described., Objectives: To describe the localization and morphologic features and determine the precise chemical composition of CUA-related calcium deposits in skin, and identify any mortality-associated factors., Design, Setting, and Participants: A retrospective, multicenter cohort study was conducted at 7 French hospitals including consecutive adults diagnosed with CUA between January 1, 2006, and January 1, 2017, confirmed according to Hayashi clinical and histologic criteria. Patients with normal renal function were excluded. For comparison, 5 skin samples from patients with arteriolosclerosis and 5 others from the negative margins of skin-carcinoma resection specimens were also analyzed., Main Outcomes and Measures: Localization and morphologic features of the CUA-related cutaneous calcium deposits were assessed with optical microscopy and field-emission-scanning electron microscopy, and the chemical compositions of those deposits were evaluated with μ Fourier transform infrared spectroscopy, Raman spectroscopy, and energy dispersive radiographs., Results: Thirty-six patients (median [range] age, 64 [33-89] years; 26 [72%] female) were included, and 29 cutaneous biopsies were analyzed. Calcific uremic arteriolopathy and arteriolosclerosis skin calcifications were composed of pure calcium-phosphate apatite. Calcific uremic arteriolopathy vascular calcifications were always circumferential, found in small to medium-sized vessels, with interstitial deposits in 22 (76%) of the samples. A thrombosis, most often in noncalcified capillary lumens in the superficial dermis, was seen in 5 samples from patients with CUA. Except for calcium deposits, the vessel structure of patients with CUA appeared normal, unlike thickened arteriolosclerotic vessel walls. Twelve (33%) patients died of CUA., Conclusions and Relevance: Calcific uremic arteriolopathy-related skin calcifications were exclusively composed of pure calcium-phosphate apatite, localized circumferentially in small to medium-sized vessels and often associated with interstitial deposits, suggesting its pathogenesis differs from that of arteriolosclerosis. Although the chemical compositions of CUA and arteriolosclerosis calcifications were similar, the vessels' appearances and deposit localizations differed, suggesting different pathogenetic mechanisms.

Some debate continues to surround the existence of neutrophilic urticaria (NU) as a nosological entity. Certain authors consider NU as a banal form of urticaria since an infiltrate predominantly made up of polynuclear neutrophils (PNN) is seen in certain cases of chronic and acute urticaria. Moreover, it has been stated that the histological appearance of chronic urticaria varies according to the time between appearance of the plaque and the performance of biopsy: the presence of PNN may occur later. According to the literature, there appear to be no specific clinical characteristics associated with the presence of PNN at histology. Most cases exhibit moderate laboratory inflammatory syndrome. Data concerning therapeutic response are contradictory: some studies have shown no significant difference in terms of therapeutic response in relation to banal urticaria, while only one study has demonstrated superior response to dapsone in the case of histologically demonstrated neutrophilic infiltrate. There does not appear to be any disease more frequently associated in the event of NU. In conclusion, the available data concerning NU are insufficient to confirm the existence of this condition. A prospective study comparing routine acute and chronic urticaria biopsies would be extremely useful to better characterise the relationships between cellular infiltrate and therapeutic response., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Objectives: Systemic sclerosis (SSc) is an autoimmune disease characterised by widespread fibrosis, microangiopathy and autoantibodies. Follicular helper T (Tfh) cells CD4 + CXCR5 + PD-1 + cooperate with B lymphocytes to induce the differentiation of plasmocytes secreting immunoglobulins (Ig). Circulating Tfh (cTfh) cells are increased in several autoimmune diseases. However, there are no data about cTfh cells and their interaction with B cells in SSc. The aim of this study was to perform a quantitative and functional analysis of cTfh cells in SSc., Methods: Using flow cytometry, we analysed cTfh cells from 50 patients with SSc and 32 healthy controls (HC). In vitro coculture experiments of sorted cTfh and B cells were performed for functional analysis. IgG and IgM production were measured by ELISA., Results: We observed that cTfh cell numbers are increased in patients with SSc compared with HC. Furthermore, the increase in cTfh cells was more potent in patients with severe forms of SSc such as diffuse SSc and in the presence of arterial pulmonary hypertension. cTfh cells from patients with SSc present an activated Tfh phenotype, with high expression of BCL-6, increased capacity to produce IL-21 in comparison with healthy controls. In vitro, cTfh cells from patients with SSc had higher capacity to stimulate the differentiation of CD19 + CD27 + CD38 hi B cells and their secretion of IgG and IgM through the IL-21 pathway than Tfh cells from healthy controls. Blocking IL-21R or using the JAK1/2 inhibitor ruxolitinib reduced the Tfh cells' capacity to stimulate the plasmablasts and decreased the Ig production., Conclusions: Circulating Tfh cells are increased in SSc and correlate with SSc severity. The IL-21 pathway or JAK1/2 blockade by ruxolitinib could be a promising strategy in the treatment of SSc., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Digital necrosis is rarer than lower limb necrosis and constitutes a medical or surgical emergency. Etiological evaluation is required. Cold agglutinin disease is a cause of digital necrosis but diagnosis is difficult., Patients and Methods: Herein we report the case of a 57-year-old man presenting recent paroxysmal acrosyndrome of the left hand subsequently complicated by digital necrosis following occupational exposure to cold in his work as a forklift driver. After etiological evaluation, a diagnosis of primary cold agglutinin disease was made. Intravenous rituximab and topical treatment resulted in complete healing., Discussion: Cold agglutinin disease is a rare type of auto-immune hemolytic anemia. Following exposure to cold, paroxysmal cutaneous signs are frequent. The disease may be either primary or secondary with B-cell lymphoproliferative disorder, auto-immune disease or infection. A thorough workup is required. To date, the treatment combining the best positive response rate and good safety is rituximab in weekly perfusions over a 1-month period., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Background: Fingolimod is an oral immunomodulator approved for relapsing-remitting multiple sclerosis. We report a case of a primary cutaneous CD30+ T-cell lymphoproliferation occurring 6 months after initiation of fingolimod. Based on a systematic literature review, the characteristics of these fingolimod-induced lymphoproliferative disorders are described., Patients and Methods: A 56-year-old woman developed cutaneous indurated and ulcerated nodular lesions 6 months after starting fingolimod for active relapsing-remitting multiple sclerosis. Histological examination of a punch biopsy sample demonstrated a polymorphous dermal infiltrate containing large atypical CD30+ cells, leading to diagnosis of primary cutaneous CD30+ anaplastic large-cell lymphoma. Chest-abdomen-pelvis CT scans were performed to rule out secondary cutaneous anaplastic large-cell lymphoma. Spontaneous clinical regression was observed and after assessing the benefit/risk ratio, it was decided to continue fingolimod under strict surveillance, with no relapse occurring by month 18., Discussion: A systematic review of PUBMED/Medline and Embase identified seven other cases of lymphoproliferative disorders occurring during fingolimod treatment, including two other cases of primitive cutaneous CD30+ lymphoproliferative disorders., Conclusion: Even if cutaneous CD30+ lymphoproliferative disorders occur only rarely during fingolimod treatment, dermatologists should nevertheless be aware of this association for which strict dermatological surveillance is required. We would also stress that these CD30+ lymphoproliferative disorders can disappear spontaneously, as in our case, even if treatment by fingolimod is continued., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Background: The histological characteristic of hypertensive leg ulcers (HLU) is the presence of "arteriolosclerosis." The pertinence of performing a skin biopsy to diagnose HLU is questionable, as cutaneous arteriolosclerosis may be related to patient comorbidities. The objective here was to evaluate the frequency of arteriolosclerosis in skin leg biopsies performed in patients without ulcer and in control patients with HLU., Methods: We performed a retrospective study between January 2013 and July 2014. Patients were included if they had undergone a deep skin biopsy on the lower limbs, in the absence of any leg ulcer. Controls were patients with typical HLU., Results: Fifty-eight patients and 6 controls were included. Hypertension was present in 25 patients (43%). Arteriolosclerosis, defined as fibrous endarteritis, was present in 35 out of 58 patients (60%) and in all of the controls. No hyalinosis or hyperplastic proliferative arteriolosclerosis was observed in the patients or controls. Only age was an independent factor associated with the presence of cutaneous arteriolosclerosis (p &x#3c; 0.0001)., Conclusion: Cutaneous arteriolosclerosis is significantly and independently associated with age. Thus, skin biopsy seems not to be necessary for the diagnosis of HLU but only for a differential diagnosis., (© 2018 S. Karger AG, Basel.)

Background: The incidence of cancer is increased in patients with systemic sclerosis (SSc). Further, recent studies have also shown that the presence of anti-RNA polymerase III antibodies is associated with a higher incidence of cancer in this population., Patients and Methods: Herein we present the cases of two men aged 56 and 23 years presenting SSc without anti-Scl70 or anti-centromere antibodies but with anti-RNA polymerase III antibodies. Clinical symptoms led us to prescribe more laboratory exams and both patients were diagnosed with cancer of the nasopharyngeal area., Discussion: Anti-RNA polymerase III antibodies are useful for SSc diagnosis in patients without anti-centromere or anti-Scl70 antibodies. Their presence must lead physicians to screen for associated cancer, even in the absence of clinical signs., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Background: Changing from one antimalarial (AM) agent to another is often recommended in cutaneous lupus erythematosus (CLE) when the first AM agent is ineffective or poorly tolerated., Objective: To evaluate the effect on cutaneous response of a switch from hydroxychloroquine to chloroquine, or the reverse, after failure of the first AM agent., Methods: We conducted a retrospective observational study between 1997 and September 2015. The overall cutaneous response rate and reasons for failure of the switch were assessed for up to 48 months. Kaplan-Meier survival curves were used to assess the risk for failure of the second AM agent., Results: A total of 64 patients with CLE (78% were women) were included; for 48 patients, the switch was for inefficacy, and for 16, it was for adverse events. Median follow-up was 42 months (range, 3-171). Of the patients changed because of inefficacy, 56% were responders at month 3; however, the response decreased over time, with a median duration before failure of the second AM agent of 9 months (95% confidence interval, 6-24). For patients switched because of adverse events, the second AM agent was well tolerated in 69% of cases., Limitations: Retrospective design and subjective evaluation of cutaneous response., Conclusion: A change of AM agent should be considered in patients with CLE when the first AM agent is ineffective or poorly tolerated., (Copyright © 2017 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate the efficacy and safety of ustekinumab in the treatment of oral ulcers (OU) in patients with Behçet's disease (BD)., Patients and Methods: Prospective study including 14 patients [median age of 39 (34; 41) years, with 71% of men] fulfilling criteria of the International Study Group for BD and with active OU resistant to colchicine. Patients received ustekinumab 90 mg (n = 11) or 45 mg (n = 3) subcutaneously at inclusion, at week 4, and every 12 weeks. The primary efficacy endpoint was the proportion of patients with complete response (CR), defined as no oral ulcer, at week 12., Results: At week 12, 64% were in CR, 21% in partial response and 14% non-responders. The median number of OU decreased from 2 [2; 4] to 1 [0; 1.25] (p = 0.0005) at week 12. Mean change from baseline to week 12 of Behçet's syndrome activity score (BSAS) was 22.8 ± 0.3 (p = 0.01). The median daily corticosteroids dose decreased from 12.5 (10; 16.3) to 5 [5; 10] mg/day (p = 0.02). Three patients reported headaches, leading to discontinuation of ustekinumab in one case. After a median follow-up of 7 [3; 12] months, 10 (71%) patients were still receiving ustekinumab and four (28%) experienced a relapse. Decreased levels of circulating IL-17 and IL-12 [median [IQR]; 3.9 [1.6; 10.6] vs. 29.2 [25.2; 42.7] pg/ml, and 29.4 [23.1; 33.3] vs. 56.1 [51.1; 64.4] pg/ml, p = 0.008 for both] were observed under ustekinumab, respectively., Conclusion: Ustekinumab seems to be efficient and safe for patient with BD and refractory OU although relapses are frequent., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Importance: Evidence for the long-term efficacy and safety of anti-tumor necrosis factor α agents (anti-TNF) in treating cutaneous sarcoidosis is lacking., Objective: To determine the efficacy and safety of anti-TNF in treating cutaneous sarcoidosis in a large observational study., Design, Setting, and Participants: STAT (Sarcoidosis Treated with Anti-TNF) is a French retrospective and prospective multicenter observational database that receives data from teaching hospitals and referral centers, as well as several pneumology, dermatology, and internal medicine departments. Included patients had histologically proven sarcoidosis and received anti-TNF between January 2004 and January 2016. We extracted data for patients with skin involvement at anti-TNF initiation., Main Outcomes and Measures: Response to treatment was evaluated for skin and visceral involvement using the ePOST (extra-pulmonary Physician Organ Severity Tool) severity score (from 0 [not affected] to 6 [very severe involvement]). Epidemiological and cutaneous features at baseline, efficacy, steroid-sparing, safety, and relapses were recorded. The overall cutaneous response rate (OCRR) was defined as complete (final cutaneous ePOST score of 0 or 1) or partial response (ePOST drop ≥2 points from baseline but >1 at last follow-up)., Results: Among 140 patients in the STAT database, 46 had skin involvement. The most frequent lesions were lupus pernio (n = 21 [46%]) and nodules (n = 20 [43%]). The median cutaneous severity score was 5 and/or 6 at baseline. Twenty-one patients were treated for skin involvement and 25 patients for visceral involvement. Reasons for initiating anti-TNF were failure or adverse effects of previous therapy in 42 patients (93%). Most patients received infliximab (n = 40 [87%]), with systemic steroids in 28 cases (61%) and immunosuppressants in 32 cases (69.5%). The median (range) follow-up was 45 (3-103) months. Of the 46 patients with sarcoidosis and skin involvement who were treated with anti-TNF were included, median (range) age was 50 (14-78) years, and 33 patients (72%) were women. The OCRR was 24% after 3 months, 46% after 6 months, and 79% after 12 months. Steroid sparing was significant. Treatment was discontinued because of adverse events in 11 patients (24%), and 21 infectious events occurred in 14 patients (30%). Infections were more frequent in patients treated for visceral involvement than in those treated for skin involvement (n = 12 of 25 [48%] vs n = 2 of 21 [9.5%], respectively; P = .02). The relapse rate was 44% 18 months after discontinuation of treatment. Relapses during treatment occurred in 35% of cases, mostly during anti-TNF or concomitant treatment tapering., Conclusions and Relevance: Anti-TNF agents are effective but suspensive in cutaneous sarcoidosis. The risk of infectious events must be considered.

Objective: Association between cancer and systemic sclerosis (SSc) has been described. However, paraneoplastic SSc is not well known. The aim of this article is to describe cases of paraneoplastic systemic sclerosis and to compare them to other cases of the literature, to find characteristics that can make suspect a paraneoplastic mechanism when SSc is diagnosed., Methods: We retrospectively analyzed patients, in our department who, over the last 15 years, presented with Raynaud's phenomenon with a diagnosis of SSc (including cancer during the period of SSc). Treatment of cancer had to be concomitted with an improvement of sclerosis and/or negativation of antinuclear antibodies. Review analysis of other cases was made with Pubmed., Results: Three patients responded to the criteria. Two of them had an ovarian cancer with peritoneal carcinomatosis and a concomitted SSc. One had a colon cancer with an ovarian metastasis diagnosed 1 year before SSc. None of them had anti-ENA antibody. One had a normal capillaroscopy. After treatment of cancer, all of them had an improvement of sclerosis and a negativation of antinuclear antibodies., Conclusion: We believe that physicians should be aware of paraneoplastic SSc when presentation of SSc is atypical: no anti-ENA (anti-SCl70 or anti-centromere) or normal capillaroscopy, in particular gynecologic cancer in women., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Compression therapy is a mandatory treatment of leg ulcers whether the goal is cure (stage C6 in the international classification for chronic venous disease) or prevention of recurrence (stage C5). Different indications for compression therapy were proposed by the French Superior Health Authority (HAS) in 2010, but new studies have modified attitudes since that time. Considering the very large number of options available, the many co-morbid conditions observed in these patients, as well as patient age and available assistance, it is important to adapt to the variable clinical and social situations encountered. One must keep in mind that a well-controlled treatment should improve trophic disorders and patient comfort. A poorly-adapted treatment with little or even deleterious effect will be abandoned by the patient., (Copyright © 2016. Published by Elsevier Masson SAS.)

Interleukin 10 (IL-10)-producing B cells (regulatory B cells [Bregs]) regulate autoimmunity in mice and humans, and a regulatory role of IL-10-producing plasma cells has been described in mice. Dysfunction of B cells that maintain homeostasis may play a role in the pathogenesis of chronic graft-versus-host disease (cGVHD) after allogeneic stem cell transplantation. Here, we found a relation between decreased Breg frequencies and cGVHD severity. An impaired ability of B cells to produce IL-10, possibly linked to poor signal transducer and activator of transcription 3 and extracellular signal-regulated kinase phosphorylation, was found in patients with active cGVHD. IL-10 production was not confined to a single B-cell subset, but enriched in both the CD24(hi)CD27(+) and CD27(hi)CD38(hi) plasmablast B-cell compartments. In vitro plasmablast differentiation increased the frequency of IL-10-producing B cells. We confirmed that allogeneic transplant recipients had an impaired reconstitution of the memory B-cell pool. cGVHD patients had less CD24(hi)CD27(+) B cells and IL-10-producing CD24(hi)CD27(+) B cells. Patients with cGVHD had increased plasmablast frequencies but decreased IL-10-producing plasmablasts. These results suggest a role of CD24(hi)CD27(+) B-cell and plasmablast-derived IL-10 in the regulation of human cGVHD., (© 2015 by The American Society of Hematology.)

Vemurafenib is a targeted therapy, used in patients with metastatic cutaneous melanoma who carry the BRAF V600E mutation, with a relative reduction of 63% in the risk of death. Several adverse events have been described previously, such as photosensitivity or squamous-cell carcinomas. Two cases of panniculitis have been reported recently with two different selective BRAF inhibitors. We report two cases of neutrophilic panniculitis in patients treated by vemurafenib for a metastatic melanoma. Clinical and biological examinations showed no indications for an immune nor an infectious cause of neutrophilic panniculitis. Thus, we believe that vemurafenib caused this panniculitis. Treatment with vemurafenib was maintained in both patients because of the clinical and radiological tumoral responses. One patient showed spontaneous recovery, whereas the other patient presented several recurrences of panniculitis. We believe that physicians should be aware of this cutaneous side effect of vemurafenib, but it should not lead to discontinuation of this treatment.

Type IV pili are crucial for the virulence of Neisseria meningitidis. PilC proteins belong to the complex protein machinery required for pili biosynthesis. The expression of the pilC1 gene is known to be induced during host cell contact and to be tightly controlled through four promoters, two transcription factors and a two-component signal transduction system. By screening of an insertional-mutant library, we identified a novel regulatory protein, i.e. NMA1805, involved in the pilC1 complex regulation. Increased transcription of gene NMA1805 was shown to result in augmented expression of the pilC1 gene, whereas abrogated expression of gene NMA1805 was associated with an absence of pilC1 induction upon contact with host cells. Moreover, we demonstrated that the NMA1805 gene displayed two promoters. The NMA1805 regulatory protein was evidenced to interact with one of them.

In order to adapt to changing environments, bacteria have evolved two-component systems (TCSs) that are able to sense and respond to environmental stimuli. The signal perception relies on a sensor protein whose activation allows rapid adaptation through transcriptional regulation achieved by the regulatory protein. The ability to adhere to and grow on the surface of human host cells is an absolute requirement for many pathogens, including Neisseria meningitidis, in order to colonize new hosts and to disseminate inside their host. Among the four TCSs encoded in the meningococcus genome, only the PhoQ (MisS)/PhoP (MisR) system has been shown to constitute a functional signal transduction circuit. To investigate the involvement of this TCS in the adaptation process requisite for host cell colonization, we have tested the ability to grow on host cells of a mutant inactivated for the sensor of the TCS. Our results demonstrate the involvement of the TCS in the adaptation of the meningococcus to growth on host cells. We show that the expression of the PhoQ (MisS)/PhoP (MisR) TCS is cell-contact controlled. Furthermore, this TCS controls the regulation of a group of genes, the REP2 regulon, previously shown to be cell-contact regulated and to encode functions crucial for the adaptation of the bacterium to host cell colonization. Thus, we provide evidence that one of the four TCSs existing in N. meningitidis contributes to the adaptation of the pathogen to growth on host cells.