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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).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.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 TBI0.75); 31% had at least a macrovascular injury associated or not with microvascular impairment (abnormal ABI) and 12.6% had a TP50 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.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.

Introduction Kikuchi-Fujimoto disease (KFD) is a self-limited histiocytic necrotizing lymphadenitis sometimes affecting the skin. “Kikuchi disease-like inflammatory pattern” (KLIP) has been described in cutaneous lesions as similar pathological features in patients without lymph node involvement and as a potential clue for the diagnosis of lupus. We aimed to describe KLIP-associated clinical and immunological features in lupus patients with a retrospective case-control study. Methods Thirteen cases of KLIP were included as well as thirty-nine age- and sex-matched control lupus patients without KLIP. At the time of KLIP diagnosis, 4/13 patients (31%) had isolated cutaneous lupus erythematosus (CLE) and 9/13 had (69%) systemic lupus erythematosus (SLE) including 6 (46%) with severe haematological, lung, cardiac or renal disease. KLIP features were observed in skin biopsies of different clinical presentations. Results Compared with our control group, KLIP patients more frequently had SLE 9/13 (69%) versus 8/39 (21%) (OR 12.9; IC95% [2.86–58.2]; p = 0.0004) and more frequently severe SLE. Two out of four CLE exhibiting KLIP lesions (50%) developed severe SLE with cardiac or renal involvement after 12 and 24 months, respectively. Treatment with thalidomide 100 mg/day allowed rapid and complete clearance of cutaneous lesions in 6/6 KLIP patients. The need to use thalidomide tended to be more frequent in KLIP patients than in controls. Conclusion Our study suggests that KLIP features in lupus skin lesions are associated with SLE and severe systemic features. Despite a limited number of isolated CLE patients with KLIP features in the skin, this observation may warrant closer follow-up on patients with a higher risk of developing SLE.

International audience; Background: Diagnosing drug reaction with eosinophilia and systemic symptoms (DRESS) is challenging. Some clinicians reject this diagnosis when the delay of onset is less than 15 days after drug intake.Objectives: To assess the delay of DRESS occurrence and culprit drugs.Methods: All patients hospitalized in 3 dermatology departments with a first occurrence of DRESS for which a drug was highly suspected were included in this retrospective study. Based on the delay in DRESS occurrence, cases were classified into 2 groups: a rapid-onset group (≤15 days after exposure) and a delayed-onset group (>15 days).Results: A total of 41 patients with DRESS were included: 14 in the rapid-onset and 27 in delayed-onset groups. In the rapid-onset group, antibiotics (n = 6/14) and iodinated contrast media (n = 5/5) were the predominant culprits. Carbamazepine (n = 4/4), lamotrigine (n = 6/6), allopurinol (n = 8/8), and sulfasalazine (n = 2/2) were exclusively found in the delayed-onset group.Limitations: The retrospective nature, limited number of participants, and lack of detailed information on previous exposure to sensitizing drugs in some instances.Conclusions: DRESS is frequently related to drugs introduced 15 or fewer days before the occurrence of cutaneous adverse reactions. The time of onset of DRESS may differ depending on the medications involved.

This is a clinical case illustrating a diagnosis of an IgG4 related-disease (IgG4-RD) diagnosed in a vascular context.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.A Raynaud phenomenon with distal arterial thrombosis is rarely observed in the IgG4-RD.

International audience

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.

Background Hypersensitivity to acetylsalicylic acid (ASA) constitutes a serious problem for subjects with coronary artery disease. In such subjects, physicians have to choose the more appropriate procedure between challenge and desensitization. As the literature on this issue is sparse, the present study aims to establish in these subjects clinical criteria for eligibility for an ASA challenge and/or desensitization. Methods Collection and analysis of data on ASA challenges and desensitizations from 10 allergy centers, as well as consensus among the related physicians and an expert panel. Results Altogether, 310 subjects were assessed; 217 had histories of urticaria/angioedema, 50 of anaphylaxis, 26 of non-immediate cutaneous eruptions, and 17 of bronchospasm related to ASA/NSAID intake. Specifically, 119 subjects had index reactions to ASA doses lower than 300 mg. Of the 310 subjects, 138 had an acute coronary syndrome (ACS), 101 of whom underwent desensitizations, whereas 172 suffered from a chronic ischemic heart disease (CIHD), 126 of whom underwent challenges. Overall, 163 subjects underwent challenges and 147 desensitizations; 86 of the latter had index reactions to ASA doses of 300 mg or less. Ten subjects reacted to challenges, 7 at doses up to 500 mg, 3 at a cumulative dose of 110 mg. The desensitization failure rate was 1.4%. Conclusions In patients with stable CIHD and histories of non-severe hypersensitivity reactions to ASA/NSAIDs, an ASA challenge is advisable. Patients with an ACS and histories of hypersensitivity reactions to ASA, especially following doses lower than 100 mg, should directly undergo desensitization. This article is protected by copyright. All rights reserved.

Background Few studies have been published on the histopathology of cutaneous adverse drug reactions (CADR), and most of these lack information on skin allergological tests. The histopathology of drug reaction with eosinophilia and systemic symptoms (DRESS) is also seldom described. The purpose of our study was to examine six types of well-documented CADR (maculopapular exanthema, DRESS, fixed drug eruption, Stevens–Johnson syndrome, toxic epidermal necrolysis [TEN], and acute generalized exanthematous pustulosis) using histopathology and immunohistochemistry to evaluate the expression of granulysin, a key molecule in TEN. Methods We retrospectively included 106 skin biopsies performed in proven cases of CADR (by chronological investigation, single attributable drug, or/and skin tests). All slides were reviewed, and microscopic changes were analyzed using a standardized form. Granulysin expression was studied by immunohistochemistry. Results In DRESS, we observed spongiosis, edema, and basal vacuolization, with rare necrotic keratinocytes and constant lymphocytic infiltrate in the superficial dermis. Eosinophils were often present, and pustules were found in 15% of cases. Necrotic keratinocytes are often absent in maculopapular exanthema. Granulysin was expressed in six types of CADR with a trend toward more intense expression in DRESS and TEN. Conclusion We detailed further about the histopathology of DRESS. Granulysin expression was observed in all CADR with a marked overlap of expression pattern between the six types.

International audience; An accurate diagnosis of β‐lactam (BL) allergy can reduce patient morbidity and mortality. Our aim was to investigate the availability of BL reagents, their use and test procedures in different parts of Europe, as well as any differences in the diagnostic workups for evaluating subjects with BL hypersensitivity. A survey was emailed to all members of the EAACI Drug Allergy Interest Group (DAIG) between February and April 2016, and the questionnaire was meant to study the management of suspected BL hypersensitivity. The questionnaire was emailed to 82 DAIG centres and answered by 57. Amoxicillin alone or combined to clavulanic acid were the most commonly involved BL except in the Danish centre, where penicillin V was the most frequently suspected BL. All centres performed an allergy workup in subjects with histories of hypersensitivity to BL: 53 centres (93%) followed DAIG guidelines, two national guidelines and two local guidelines. However, there were deviations from DAIG recommendations concerning allergy tests, especially drug provocation tests. A significant heterogeneity exists in current practice not only among countries, but also among centres within the same country. This suggests the need to re‐evaluate, update and standardize protocols on the management of patients with suspected BL allergy.

International audience; BACKGROUND:In this retrospective study, we investigated the impact of 68 Ga-PSMA-11 PET-CT (PSMA PET-CT) upon the treatment plan and therapeutic response obtained for Prostate Cancer (PCa) patients presenting an occult biochemical recurrence.METHODS:Forty-two patients with previously negative or doubtful 18F-Choline (FCH) were enrolled. PET images were recorded 1 h after injection of tracer. Only a few months after treatment ended, a PSA assay was requested to evaluate the therapeutic efficacy of the treatment based on PSMA results.RESULTS:PSMA-positive lesions were detected in 34/42 (80.9%) patients. Detection rates were 85.7% and 89.3% for serum PSA levels lower than 2 ng/mL, and >2 ng/mL, respectively. One hundred seventy-three lesions were detected: 132/173 in lymph nodes (76.3%), 22/173 as metastatic sites (bone or lung) (12.7%), and 19/173 in the prostate bed (10.9%). As a result of the PSMA PET-CT, therapeutic management changed in 31/42 patients (73.8%). With a follow-up of 4.9 ± 2.27 months, 32/42 (76.2%) PSA assays after treatment guided by PSMA PET-CT were collected. For 37.5% (12/32) of patients, the serum PSA level was lower than 0.2 ng/mL and a PSA decrease of over 50% in 8 (25.0%) other patients were obtained.CONCLUSION:Performing a PSMA PET-CT when FCH PET-CT was doubtful or negative allows the recurrence localization in more 80% of patients and this had a major clinical impact, as it resulted in treatment change in more than 70% of patients as well as a significant decrease in PSA levels in more than 60% of them.

INTRODUCTION: Ultrasonic detection of venous gas emboli (VGE) in the precordial (PRE) region is commonly used in evaluation of decompression stress. While subclavian (SC) VGE detection can also be used to augment and improve the evaluation, no study has rigorously compared VGE grades from both sites as decompression stress indicators. METHODS: This retrospective study examined 1,016 man-dives breathing air extracted from the Defence Research and Development Canada dataset. Data for each man-dive included dive parameters (depth, bottom time, total ascent time), PRE and SC VGE grades (Kisman-Masurel) and post-dive decompression sickness (DCS) status. Correlation between SC and PRE grades was analyzed and the association of the probability of DCS (pDCS) with dive parameters and high bubble grades (HBG III- to IV) was modelled by logistic regression for SC and PRE separately for DCS risk ratio comparisons. RESULTS: PRE and SC VGE grades were substantially correlated (R = 0.66) and were not statistically different (P = 0.61). For both sites, pDCS increased with increasing VGE grade. When adjusted for dive parameters, the DCS risk was significantly associated with HBG for both PRE (P = 0.03) and SC (P < 0.001) but the DCS risk ratio for SC HBG (RR = 6.0, 95% CI [2.7–12.3]) was significantly higher than for PRE HBG (RR = 2.6, 95% CI [1.1–6.0]). CONCLUSIONS: The association of bubble grades with DCS occurrence is stronger for SC than PRE when exposure severity is taken into account. The usefulness of SC VGE in decompression stress evaluation has been underestimated in the past.

Aims Linear immunoglobin A (IgA) bullous dermatosis is a rare autoimmune dermatosis considered spontaneous or drug-induced (DILAD). We assessed all DILAD cases, determined the imputability score of drugs and highlighted suspected drugs. Methods Data for patients with DILAD were collected retrospectively from the French Pharmacovigilance network (from 1985 to 2017) and from physicians involved in the Bullous Diseases French Study Group and the French Investigators for Skin Adverse Reactions to Drugs. Drug causality was systematically determined by the French imputability method. Results Of the 69 patients, 42% had mucous membrane involvement, 20% lesions mimicking toxic epidermal necrolysis (TEN), 21% eosinophil infiltrates and 10% keratinocytes necrosis. Direct immunofluorescence, in 80%, showed isolated linear IgA deposits. Vancomycin (VCM) was suspected in 39 cases (57%), 11 had TEN-like lesions, as compared with three without VCM suspected. Among the 33 patients with a single suspected drug, 85% had an intrinsic imputability score of I4. Among them, enoxaparin, minocycline and vibramycin were previously unpublished. For all patients, the suspect drug was withdrawn; 15 did not receive any treatment. First-line therapy for 31 patients was topical steroids. Among the 60 patients with available follow-up, 52 achieved remission, 10 without treatment. Four patients experienced relapse, four died and five had positive accidental rechallenges. Conclusions There is no major clinical difference between DILAD and idiopathic linear IgA bullous dermatosis, but the former features a higher prevalence of patients mimicking TEN. VCM, suspected in more than half of the cases, might be responsible for more severe clinical presentations. We report three new putative drugs.

International audience

Background Omalizumab is approved as an add-on therapy for the treatment of chronic spontaneous urticaria (CSU) in patients with inadequate response to H1-antihistamine treatment. The urticaria control test (UCT) is a reliable, concise tool developed as an alternative to the 7-day urticaria activity score (UAS7) - the standard for CSU disease activity assessment. Objectives This prospective, open-label, phase IV study evaluated the efficacy and safety of omalizumab in French adult patients with CSU nonresponsive to H1-antihistamine treatment. Materials and methods Patients [n = 136; stratified 1 : 2 (with angio-oedema : without angioedema)] received omalizumab 300 mg subcutaneously every 4 weeks for 12 weeks. Study assessments included UCT, UAS7, angio-oedema activity score and d-dimer levels (exploratory objective). Results At Week 12, 74·6% of the patients achieved disease control [UCT score ≥ 12 (primary endpoint)] and 67·7% of patients showed well-controlled disease (UAS7 ≤ 6). There was a strong negative correlation between UCT score and UAS7 at Week 12 (Spearman's correlation coefficient -0·839). Mean plasma d-dimer concentration was elevated at baseline (1002·1 ng mL-1 ) and decreased notably at Week 8 (455 ng mL-1 ). Among the nine patients with a very high baseline d-dimer concentration (> 3000 ng mL-1 ), eight were responders (UAS7 ≤ 6) at Week 12. Conclusions Omalizumab was efficacious in patients with CSU nonresponsive to H1-antihistamines. The UCT was a reliable tool for disease assessment and the scores correlated well with UAS7. This study does not support the usefulness of d-dimer to monitor long-term disease prognosis in adult urticaria; however, it may indicate patients who respond to omalizumab.

International audience; BackgroundArgan is used worldwide in numerous cosmetic products, as this fruit is supposed to have many beneficial properties on health. New cases of allergy can be expected with the growing use of argan. We investigated all workers (9) employed by a cosmetic factory and exposed to argan powder to identify possible allergies related to exposure to argan powder.MethodsPatients were investigated in the occupational disease department and, according to their symptoms, underwent pulmonary function testing, methacholine challenge, specific inhalation challenge to argan powder, skin prick tests, and immunoblotting analysis.ResultsWe report three cases of occupational asthma to argan powder and a probable case of rhinitis. Fifteen argan proteins were recognized by the patients' IgE. Identification of proteins, cross-reactions to nuts, and ELISA inhibition tests suggested that some argan allergens can cross-react in vitro with hazelnut allergens, including 11S globulin and vicilin.ConclusionHigh-level exposure to argan powder should be considered to be a potential cause of IgE-mediated allergy, and workers handling argan powder should be carefully investigated.

Infliximab (IFX) is used for the treatment of inflammatory bowel diseases (IBD). Immediate hypersensitivity reactions (HR) to IFX are frequently reported.We investigated immunoglobulin E (IgE)-mediated mechanisms underlying immediate HR to IFX. We also evaluated the clinical utility of allergological tests as well as the tolerability of IFX retreatment in these patients.This was a prospective single-center study including IBD patients with previous immediate HR to IFX. Skin tests to IFX, including prick tests and intradermal tests, and measurement of anti-IFX IgE antibodies were performed at least 4 weeks after HR. In case of negative skin tests and absence of IgE antibodies, readministration of IFX was performed with a twice-reduced infusion rate. In case of positive tests or recurrence of HR during readministration of IFX, a 12-step desensitization or induction of tolerance protocol was proposed.A total of 24 IBD patients were included (Crohn's disease: n=20). Prick tests to IFX were all negative. Intradermal test was positive in one patient. Anti-IFX IgE antibodies were not detected in 21 patients and were detected in three patients (significant level in one patient and intermediate level in two patients). No relationship was observed between positive skin tests and the presence of anti-IFX IgE antibodies. Switch to adalimumab was well tolerated in 10/11 patients. The readministration of IFX was well tolerated in 4/11 patients. Desensitization to IFX was successful in three out of four patients.The vast majority of immediate HR to IFX is not IgE-mediated. Allergological tests are of poor clinical utility. Desensitization or induction of tolerance protocol may allow continuation of IFX therapy in IBD patients with a history of immediate HR.

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.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.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.

Background Eyelids are frequent sites of contact dermatitis. No prospective study focused on eyelid allergic contact dermatitis (EACD) has yet been published, and this topic has never been studied in French patients. Objectives To prospectively evaluate the usefulness of an eyelid series in French patients patch tested because of EACD, and to describe these patients. Methods We prospectively analysed standardized data for all patients referred to our departments between September 2014 and August 2016 for patch testing for suspected EACD as the main reason. All patients were patch tested with an eyelid series, the European baseline series (EBS), the French additional series, and their personal products. Patch testing with additional series and repeated open application tests (ROATs) or open tests were performed if necessary. A standardized assessment of the relevance was used, and the analysis of the results was focused on patients having positive test results with a current certain relevance. Results Two-hundred and sixty-four patients (238 women and 26 men) were included. Three-hundred and twenty-two tests gave positive results in 167 patients, 84 of whom had currently relevant reactions: 56 had currently relevant positive test reactions to the EBS, 16 had currently relevant positive test reactions to their personal products, 8 had currently relevant positive test reactions to the French additional series, and 4 had currently relevant positive test reactions to the eyelid series. Sixty-seven per cent of all relevant cases were related to cosmetic products. The most frequent allergens with current relevance were methylisothiazolinone (10.2%), fragrance mix I (3%), nickel (2.7%), hydroxyperoxides of linalool (2.7%) and limonene (2.3%), and Myroxylon pereirae (2.3%). Current atopic dermatitis was found in 9.5% of patients. The duration of dermatitis was shorter (23.2 vs 34.2 months; P = .035) in patients with currently relevant test reactions. The percentage of currently relevant tests remained the same when atopic patients or dermatitis localized only on the eyelids were taken into account. Conclusion In French patients, testing for EACD with the extended baseline series and personal products, also including ROATs and use tests, appears to be adequate, considering the currently relevant positive test reactions. The regular addition of an eyelid series does not seem to be necessary.

Background There are few population-based studies assessing the prevalence of skin diseases. Objectives To estimate the prevalence of five chronic skin inflammatory diseases, i.e. atopic dermatitis (AD), psoriasis, alopecia areata (AA), vitiligo and hidradenitis suppurativa (HS) in France, using validated self-diagnostic questionnaires. Methods Population-based study using a representative sample of the French general population aged more than 15 years and sampling with replacement design. All participants were asked (ii) to fill in a specific questionnaire including socio-demographic characteristics, (ii) to declare if they have been diagnosed with one or more skin problem or skin diseases during their life, and (iii) to fill in five validated self-reported questionnaires for AD, psoriasis, AA, vitiligo and HS. Results A total of 20.012 adult participants responded to the questionnaire of whom 9760 were men (48.8%) and 10.252 (51.2%) were women. We identified a prevalence of 4.65% for AD (931 individuals), 4.42% for psoriasis (885 individuals), 1.04% for AA (210 individuals), 0.46% for vitiligo (93 individuals) and 0.15% for HS (29 individuals), respectively. Limitations Questionnaire-based study and possible disease misclassifications. Conclusion This is the largest population-based study aiming to estimate the prevalence of five chronic skin inflammatory diseases.

International audience; BACKGROUND: Atopy has emerged as a major determinant of airway inflammation.OBJECTIVE: To examine whether early markers of occupational asthma increase with degree of sensitisation.METHOD: This study was a prospective follow-up study of apprentices in baking, pastry-cooking and hairdressing during their 2-year apprenticeship. Four visits were conducted to administer a standardised questionnaire, a methacholine challenge test to assess bronchial hyperresponsiveness (BHR) and to measure fractional exhaled nitric oxide (FeNO). Degree of sensitisation was estimated based on the number of positive skin prick tests (SPTs) for 12 common allergens. Mixed-effect models were applied to examine the association between the degree of sensitisation and FeNO levels, BHR and eosinophilic status (more than 3% of cells in nasal lavage fluid).RESULTS: Of the 441 apprentices who agreed to take part in the study, 417 had at least one SPT session providing usable results. Degree of sensitization was related to BHR and FeNO levels. Compared to non-sensitised subjects, FeNO levels were 83% higher (P < 0.01) in highly sensitised subjects and 30% higher (P < 0.01) in weakly sensitised subjects. However, the degree of sensitisation was not predictive of the evolution of these markers.CONCLUSION: Degree of sensitisation is related to early markers of airway inflammation.

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.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.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.

Our aim was to assess the prevalence of adverse effects (AEs) pertaining to the use and withdrawal of hydroxychloroquine (HCQ) in dermatological outpatients.We conducted a retrospective study between January 2013 and June 2014 that included consecutive patients currently or previously receiving HCQ seen in our department. AEs were collated using a standardized questionnaire and validated by clinical and laboratory examination. Drug causality was evaluated using the updated French drug reaction causality assessment method. The main evaluation criterion was the prevalence of AEs in which HCQ had an intrinsic imputability score of I2.We included 102 patients (93 of whom were women, with a median age of 44.5; range: 22-90years). HCQ was given for cutaneous lupus in most cases (n=70). At least one AE was reported for 55 patients. Among the 91 reported AEs, 59 (65%) had an HCQ intrinsic imputability score I2. AEs were responsible for permanent HCQ discontinuation in 19 cases. Of these, 8 were unrelated to HCQ based on imputability score. The most common AEs associated with HCQ were gastrointestinal and cutaneous signs. Of the 8 patients diagnosed with retinopathy, only 3 were confirmed after reevaluation.AEs associated with HCQ were reported for over 50% of patients and were responsible for permanent HCQ discontinuation in one-third of cases. A more in-depth evaluation of imputability seems necessary, particularly regarding ophthalmological symptoms, since in two thirds of cases the reasons for discontinuation were not related to HCQ.

Assessment of the efficacy and safety of omalizumab in chronic urticaria refractory to conventional treatment (H1-antihistamines at high dosage and montelukast) in real-life practice.A retrospective, descriptive, single-centre study was performed of the data for all patients presenting refractory chronic spontaneous urticaria or inducible urticaria and receiving omalizumab (300mg every four weeks) from November 2012 to June 2016.In all, 23 patients were included. Omalizumab led to complete or significant remission in 19 patients (83%) with chronic urticaria, with remission in 9 patients (47%) occurring within 72hours of the first injection. One patient had a partial response and 3 (13%) showed no response. Only 2 patients (9%) in complete remission stopped their treatment at 1 and 3 years. 52% of patients presented non-serious adverse events, which in one case resulted in treatment withdrawal.Omalizumab exhibited good real-life efficacy in a small series of chronic urticaria patients in France.

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.

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.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.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.

The rate of hypersensitivity reactions to platinum salts (PS) and taxanes (TX) is on the increase. The aim of our study was to show the value of skin testing and efficacy of rapid drug desensitization.This was a retrospective study conducted between January 2007 and February 2016 in patients consulting for immediate or delayed hypersensitivity to PS and TX. Skin prick tests (pT) and intradermal reaction tests (IDR) were performed according to the ENDA/EAACI recommendations. We used a 12-step desensitization protocol for rapid drug desensitization.Among the 99 patients included (30 men, 69 women, age 60.4) PS were suspected in 86 cases and taxanes in 13 cases. Skin tests were positive in 25 patients (7 pT, 18 IDR), 23 for platinum salts and 2 for taxanes. Rapid drug desensitization was proposed in 50 patients and performed in 33 (30 PS and 3 TX), proved effective in 29 patients, with protocol adaptation being necessary in 7 cases, and was ineffective in 4 patients. The skin tests for the latter 4 patients were positive. Seventy-five percent of patients with positive skin tests to oxaliplatin presented hypersensitivity reactions during desensitization, i.e. twice as many as patients having negative skin tests. Two percent of patient for PS and 7% for TX had cross reactivity.This French study confirms the efficacy of the 12-step protocol that allows patients to receive chemotherapy after hypersensitivity reaction. Skin test permits the detection of cross-reactions but their practice must be considered based on the patient's history.

A 10-year-old male presented with complaints of yellowish papules on his neck. At the age of five years, he had abdominal pain and haemorrhagic diarrhoea with high levels of anti-transglutaminase and anti-endomysium antibodies, and negative hypercoagulable workup. The endoscopic examination of an intestinal biopsy showed subtotal villous atrophy, crypt hyperplasia, and lymphocyte infiltration of crypts, which confirmed the diagnosis of coeliac disease. The patient's mother noticed the appearance [...]

Background. Airborne allergic contact dermatitis caused by paints containing isothiazolinones has been recognized as a health hazard. Objectives. To collect epidemiological, clinical and patch test data on airborne allergic contact dermatitis caused by isothiazolinone-containing paints in France and Belgium. Methods. A descriptive, retrospective study was initiated by the Dermatology and Allergy Group of the French Society of Dermatology, including methylchloroisothiazolinone (MCI)/methylisothiazolinone (MI)-and/or MI-sensitized patients who developed airborne allergic contact dermatitis following exposure to isothiazolinone-containing paint. Results. Forty-four cases were identified, with mostly non-occupational exposure (79.5%). Of the patients, 22.5% of also had mucosal symptoms. In several cases, the dermatitis required systemic corticosteroids (27.3%), hospitalization (9.1%), and/or sick leave (20.5%). A median delay of 5.5 weeks was necessary to enable patients to enter a freshly painted room without a flare-up of their dermatitis. Approximately one-fifth of the patients knew that they were allergic to MI and/or MCI/MI before the exposure to paints occurred. Conclusion. Our series confirms that airborne allergic contact dermatitis caused by paints containing isothiazolinones is not rare, and may be severe and long-lasting. Better regulation of isothiazolinone concentrations in paints, and their adequate labelling, is urgently needed.

International audience; SETTING: Occupational asthma (OA) is most likely to develop in the very early years of exposure. OBJECTIVE: To describe the early incidence of OA among bakers/pastry-makers (BP) and hairdressers and to explore the role of atopy. DESIGN: Following a retrospective follow-up design, subjects were invited to undergo telephone interviews. Those who declared work-related respiratory or rhinitis symptoms and a sample group of others were offered a medical visit for OA investigations. Data from interviews and from medical visits were used to estimate the incidence of OA according to increasing durations of exposure. RESULTS: A total of 866 subjects were interviewed (mean age 25.3 years, 43.8% females), of whom 282 underwent a medical visit. Total estimated incidence rates of 'confirmed or probable' OA during the first 12 years of exposure were high in BP (2.63 per 100 person-years [py]) and in hairdressers (0.58/100 py), particularly in the first 4 years. Atopy is a strong risk factor for incidence among BP but, irrespective of the occupational sector, it does not influence the timing of OA symptoms. CONCLUSION: OA symptoms occur soon after the start of exposure. Our results suggest that atopy does not precipitate the occurrence of symptoms in two different allergen exposure settings.

To evaluate the vaccine coverage of psoriasis patients prior to initiating or changing immunosuppressant therapy, and to verify that the prescribed vaccines have been administered.We conducted a bi-centre, observational, cross-sectional study over 9 months. Psoriasis patients in whom immunosuppressant therapy (comprising cyclosporine, methotrexate, etanercept, infliximab, adalimumab or ustekinumab) was indicated were included. Medical history, previous treatments, vaccination status, viral serology results (for hepatitis B, measles, and chickenpox), and reasons for non-vaccination were assessed via questionnaire.Sixty-eight patients were included. One third brought their immunization records. Overall, 54.4% had already received immunosuppressant therapy; of these, 9 were up to date for influenza and 3 were up to date for pneumococcus. Only one patient was up to date for all of the recommended vaccinations. A total of 61% of patients were seronegative for hepatitis B. The following vaccines were updated: DTP (in 2 patients), DTP-pertussis (12), influenza (22), pneumococcus (45), and hepatitis B (6). None of the three patients with plans to travel to yellow fever-endemic countries had been vaccinated. In all, 53 (78%) stated that they had already had chickenpox and 43 (63.2%) stated that they had had one of the following three diseases: measles, rubella, or mumps. Fifty-two patients were serologically tested for chickenpox, and 98% were immunized. The most common reasons for not updating the immunization schedule were the absence of any notification or proposal by the patient's doctor and oversight.This study should help raise awareness among patients and health professionals concerning the new vaccination recommendations for a population particularly at risk of infection.

International audience; Cold contact urticaria (CCU) is a physical urticaria, also called inducible urticaria, which is triggered by exposure of the skin to cold air, surfaces or fluids. Clinical manifestations of CCU range from mild, localized whealing to life-threatening anaphylactic shock. CCU is mostly idiopathic (primary), but in rare cases it is secondary to infectious disease, with or without cryoproteins. We report here, for the first time, 4 cases of CCU that developed following vaccination, which suggests a link between these events.

International audience; BACKGROUND:Biotherapies or targeted therapies are fairly new treatments indicated for moderate to severe psoriasis. The side effects appear to be mainly infectious or cancerous. The role of biotherapies in the development of a pre-cancerous condition, monoclonal gammopathy of undetermined significance (MGUS), has recently been debated in the literature.OBJECTIVES:To evaluate the incidence of MGUS in psoriasis patients treated with biotherapy.MATERIALS AND METHODS:This study was a French multicenter retrospective study carried out through the French multicenter study group RESOPSO. Data on the results of serum protein electrophoreses performed before and within at least six months after the start of the biotherapy were collected. Demographic data, medical history, and psoriasis treatment history were specified.RESULTS:Four hundred and forty three patients were eligible for inclusion. Of these, three presented with monoclonal gammopathy for which the assessment was in favor of MGUS. The average treatment period was 19.7 months. Six patients presented with MGUS prior to the treatment. These patients' immunoglobulin levels remained stable, with an average remission of 24 months. Only psoriatic rheumatism appeared to be statistically linked to MGUS.CONCLUSION:The incidence and frequency of MGUS in psoriasis patients treated with biotherapy do not appear to increase relative to the general population.

Leukocytoclastic vasculitis is characterized by necrotizing inflammation around small blood vessels, composed mainly of neutrophils. Skin lesions in leukocytoclastic vasculitis are polymorphous, but a rare annular variant exists of which dermatologists must be aware. Herein we present a new case of this entity.We report the case of a 74-year-old man who developed annular purpuric infiltrated lesions mainly on the lower limbs, with leukocytoclastic vasculitis being confirmed by histology. This annular leukocytoclastic vasculitis regressed spontaneously with no recurrence after 6 months. The aetiology was not established.Annular leukocytoclastic vasculitis is rare, and the mechanisms underlying annularity and peripheral spread as well as the aetiology remain unexplained. This form of vasculitis with unusual clinical features may constitute a new entity in the subclass of immune complex small vessel vasculitis within the Chapel Hill classification. While the aetiology and physiopathology of this vasculitis are unknown, despite the possibility of recurrence, skin involvement appears isolated and the condition carries a good prognosis.

Dermatomyositis (DM) is an inflammatory disease associated with auto-antibodies in 50 to 70% of cases. A new antibody, anti MDA-5, has been described in association with a specific type of DM involving severe interstitial lung disease and minimal muscle disease. We report the first case of DM with MDA-5 antibodies and with interstitial lung disease and rapidly extensive digital necrosis.A 28-year-old male was hospitalized for asthenia, myalgia and subacute dyspnea. Examination demonstrated skin lesions with edema on every digit associated with purpuric and cyanotic lesions, as well as erythematous papules on the helix and the elbows, and Gottron's papules. Systemic corticosteroid therapy was initiated. The immunoprecipitation results indicated the presence of anti-MDA-5 antibodies. Despite corticosteroid therapy, the patient's respiratory status gradually deteriorated towards pulmonary fibrosis and rapidly extensive necrosis appeared on all fingers and toes. Theses effects were resistant to cyclophosphamide and immunoglobulin but were stabilized by cyclosporine.Anti-MDA-5 antibodies are specific to DM and constitute a risk factor for severe interstitial lung disease (70% of cases) with a higher risk of mortality (40%). The cutaneous presentation of this DM is specific with palmar papules and mucocutaneous ulceration. Rapidly extensive digital necrosis has not been previously reported. No treatment has demonstrated superiority.We report the first case of DM with anti-MDA-5 antibodies involving interstitial lung disease and massive digital necrosis. Because of the pulmonary risk, in the presence of clinical lesions containing anti-MDA-5 DM, screening for these antibodies should be carried out.

Background Post-excisional brachytherapy with Iridium 192 is a treatment of keloids scars (KS). Its indications and its parameters are not subject to any consensus. Objective We wanted to assess the effectiveness and satisfaction of patients treated in our centre. Patients and Methods This was a retrospective study conducted from November 2006 to November 2007. Patients with clinically and histologically proven KS treated between 1990 and 2005, were convened in consultation between September and October 2007. Clinical data and parameters of the brachytherapy have been collected. Results Eighty-seven patients (138 KS) were treated. Eighty-two KS (46 patients) met the criteria for inclusion. Thirty-two patients (55 KS) have been seen in consultation. The average time between the onset of KS and treatment was 63.5 months. The brachytherapy has begun after a maximum of 7 hours posterior to surgery for all KS. The average dose was 17.9 Gy calculated at 5 mm. We observed 23.6% of recurrence after treatment. Seventy-nine per cent of itching and 87.5% of pain have totally disappeared. The phototypes 5 and 6 had an increased risk of reccurence. Discussion This is the most important series of KS treated with Post-excisional brachytherapy presented so far. The technique is efficient in preventing keloid reccurence and in treating the functional signs, but at the expense of an unaesthetic result, of wich patient must be warned about. A follow-up of at least two years after treatment is recommended. Conflicts of interest None declared

BACKGROUND: Iodinated contrast media cause both immediate and nonimmediate hypersensitivity reactions. The aim of this prospective study was to determine the specificity and sensitivity of skin tests in patients who have experienced such reactions. METHODS: Skin prick, intradermal and patch tests with a series of contrast media were conducted in 220 patients with either immediate or nonimmediate reaction. Positive skin tests were defined according to internationally accepted guidelines. Seventy-one never-exposed subjects and 11 subjects who had tolerated contrast medium exposure, served as negative controls. RESULTS: Skin test specificity was 96-100%. For tests conducted within the time period from 2 to 6 months after the reaction, up to 50% of immediate reactors and up to 47% of nonimmediate reactors were skin test positive. For immediate reactors, the intradermal tests were the most sensitive, whereas delayed intradermal tests in combination with patch tests were needed for optimal sensitivity in nonimmediate reactors. Contrast medium cross-reactivity was more common in the nonimmediate than in the immediate group. Interestingly, 49% of immediate and 52% of nonimmediate symptoms occurred in previously unexposed patients. Many of these patients were skin test positive, indicating that they were already sensitized at the time of first contrast medium exposure. CONCLUSIONS: These data suggest that at least 50% of hypersensitivity reactions to contrast media are caused by an immunological mechanism. Skin testing appears to be a useful tool for diagnosis of contrast medium allergy and may play an important role in selection of a safe product in previous reactors.

Background: Currently used antimalarial drugs (AM) are hydroxychloroquine and chloroquine, which are prescribed for many autoimmune disorders. The value of skin tests on cutaneous adverse drug reactions (CADR) with AM remains unknown. Objective: The main objective of this retrospective study is to know whether skin tests for AM are useful and how to manage the recovery of AM therapy in these patients. Methods: All patients referred for suspected CADR secondary to AM between 2001 and 2014 in eight French dermatology centers were retrospectively reviewed. Results: We report herein a retrospective series of 20 patients with CADR and AM involvement. Skin tests, performed in 14/20 patients, were negative in all cases. Six patients had an oral provocation test with recurrence of CADR in 1 case. Conclusion: We encourage dermatologists to perform oral provocation tests in nonsevere CADR in order to allow AM rechallenge at progressive doses.

International audience; OBJECTIVES:The broader and prolonged use of anti-tumor necrosis factor (TNF) agents in inflammatory bowel disease (IBD) could expose patients to an increased risk of adverse reactions, including dermatological complications. We assessed the cumulative incidence of anti-TNF-induced cutaneous adverse reactions in IBD patients, their risk factors, their dermatological management, and their outcome in a large cohort of IBD patients.METHODS:In a single-center observational retrospective study, including all consecutive adult IBD patients treated with an anti-TNF agent between 2001 and 2014, all patients with dermatological complications under anti-TNF therapy were identified in a well-defined cohort of IBD patients. We conducted a survival analysis to determine the cumulative incidence of dermatological complications and risk factors for developing any dermatological complications, cutaneous infections, and psoriasiform lesions. Survival curves were estimated by the Kaplan-Meier method, and we used a Cox proportional hazards model to test the association between parameters and time to each event: any dermatological complication, cutaneous infections, and psoriasis lesions.RESULTS:Among 583 IBD patients, 176 dermatological complications occurred, involving 20.5% of patients. Median duration of follow-up was 38.2 months (range: 1-179). Psoriasiform lesions (10.1%; 59/583) and cutaneous infections (11.6%, 68/583) were the most frequently observed, with a cumulative incidence of, respectively, 28.9% and 17.6% at 10 years. They led to anti-TNF discontinuation, respectively, in 18.6% and 2.9% of patients. In case of switching to another anti-TNF agent for psoriasiform lesions, recurrence occurred in 57% of patients. Ulcerative colitis was associated with a lower risk of developing cutaneous infections than Crohn's disease (hazard ratio (HR)=0.25; 95% confidence interval (CI)=0.09-0.68; P=0.007). Higher dosing of anti-TNF agent was associated with a higher risk of developing cutaneous infections (HR=1.99; 95% CI=1.09-3.64; P=0.025). A younger age at time of anti-TNF initiation was associated with a higher risk of dermatological complications (HR=2.25; 95% CI=1.39-3.62; P

Modern dressings (MDs) may have a low sensitization rate, but there is a lack of prospective studies in patients with chronic leg ulcers (CLUs) to evaluate this.To determine the rate of sensitization (contact allergy) to MDs and substances present in dressings.A prospective multicentre study was carried out in patients with CLUs at five French dermatology departments; patch tests were performed with the European baseline series and with an additional 27 individual allergens and 10 MDs.Among 354 patients (226 women and 128 men) with CLUs, 59.6% had at least one positive patch test reaction to an MD and 19% had at least one sensitization to an MD. The number of positive test reactions per patient was correlated with the duration of ulcerative disease, but not with ulcer duration, the cause of the ulcer, or the presence of surrounding eczematous lesions. For 11 of 45 patients sensitized to Ialuset cream®, more detailed information could be obtained with sensitization to sodium dehydroacetate (5 cases) or Lanette SX® (3 cases).Sensitization to MDs is not rare. It is absolutely necessary to label all components of MDs on their packaging and to avoid some sensitizing molecules, such as colophonium derivatives or any strong sensitizers.

Objective: To assess the efficacy of the topical application of morphine on painful chronic skin ulcers. Method: A prospective bi-centric controlled double-blind randomised study was conducted involving 24 patients with painful chronic skin ulcers using topically applied morphine versus placebo. Ten milligrams of morphine hydrochloride with Intrasite Gel or Intrasite Gel with placebo were applied daily for five days. All patients were treated with a level II analgesic treatment. A numeric pain scale lower than 4/10 and no need for a ‘rescue’ treatment (morphine sulphate) indicated that the treatment was successful. Local and systemic tolerance of the treatments was analysed daily. Results: Twenty-four patients were included in the study, but only 18 started the protocol. Only 2/11 patients were completely relieved in the morphine group compared with 1/7 in the placebo group. Local and general tolerance of morphine was good. The peripheral efficacy of morphine is under discussion. Conclusion: The results suggest that topical morphine cannot be an alternative to morphine administered by other routes (subcutaneously or orally) in painful chronic skin ulcers. Stimulation of peripheral morphine receptors by systemic morphine could explain the difference between these results and those of previous studies. Declaration of interest: This study was supported by the University Hospital of Nancy and the Association Lorraine d’Etude et de Recherche en Dermatologie, France.

Delayed reactions to radio-contrast media (RCM) with positive skin tests are rare. We report the study of a series of 15 patients who presented delayed reactions to RCM, with an analysis of the clinical features and the results of standardized drug skin tests. Patch tests were performed with RCM and iodized antiseptics (IAs). If negative, prick tests were performed, followed by intradermal tests (IDTs), then intravenous administration under hospital surveillance. The main clinical features were maculopapular rashes or a macular rubella-like rashes. Patch tests were positive with RCM in 2 of 15 cases and with IAs in 4 of 15 cases. All the prick tests were negative. IDTs were positive at 24 h in 8 of 15 cases. 5 of 12 patients had a non-severe relapse of the rash upon receiving an RCM despite clearly negative skin tests with the readministered RCM. Visipaque cross-reacted with Iopamiron, Iomeron, Telebrix, Omnipaque, Xenetix and Hexabrix. Omnipaque cross-reacted with Hexabrix and Iopamiron. IDTs with delayed readings are of better value than patch tests in such patients. The readministration of RCM with negative IDTs must be performed with progressive amounts under hospital surveillance. Cross-reactions between various classes of RCM are frequent. The responsible epitopes are unknown. Iodine itself could be involved.