Search

Submitted by (omml@ubi.pt) on 2021-07-05T10:47:24Z No. of bitstreams: 1 2021_Bousquet J_A_COVID anaphylaxis.pdf: 12561118 bytes, checksum: 2f801ee76ad2cb3cbdaa02ffabea8e09 (MD5) Approved for entry into archive by Pessoa (pfep@ubi.pt) on 2021-07-05T10:49:11Z (GMT) No. of bitstreams: 1 2021_Bousquet J_A_COVID anaphylaxis.pdf: 12561118 bytes, checksum: 2f801ee76ad2cb3cbdaa02ffabea8e09 (MD5) Rejected by Pessoa (pfep@ubi.pt), reason: Rever os nomes dos autores. Depois da correção é só voltar a submeter. on 2021-07-05T10:54:19Z (GMT) Submitted by (omml@ubi.pt) on 2021-07-05T11:52:24Z No. of bitstreams: 1 2021_Bousquet J_A_COVID anaphylaxis.pdf: 12561118 bytes, checksum: 2f801ee76ad2cb3cbdaa02ffabea8e09 (MD5) Approved for entry into archive by Pessoa (pfep@ubi.pt) on 2021-07-05T13:34:51Z (GMT) No. of bitstreams: 1 2021_Bousquet J_A_COVID anaphylaxis.pdf: 12561118 bytes, checksum: 2f801ee76ad2cb3cbdaa02ffabea8e09 (MD5) Approved for entry into archive by Pessoa (pfep@ubi.pt) on 2021-07-05T13:35:49Z (GMT) No. of bitstreams: 1 2021_Bousquet J_A_COVID anaphylaxis.pdf: 12561118 bytes, checksum: 2f801ee76ad2cb3cbdaa02ffabea8e09 (MD5) Made available in DSpace on 2021-07-05T13:35:49Z (GMT). No. of bitstreams: 1 2021_Bousquet J_A_COVID anaphylaxis.pdf: 12561118 bytes, checksum: 2f801ee76ad2cb3cbdaa02ffabea8e09 (MD5) Previous issue date: 2021-04-02 info:eu-repo/semantics/publishedVersion

The term Sneddon's syndrome (SS) has been used since 1965 to describe a vasculopathy characterized by a combination of cerebrovascular disease with livedo racemosa. SS may be classified as antiphospholipid+ (aPL+) or antiphospholipid- (aPL-). Little is known about aPL- SS; in this review we describe the epidemiology and pathogenesis of aPL- SS, as well as the clinical and histologic features. We discuss recent findings in terms of neurologic and cardiac involvement. Moreover, differential diagnoses of conditions that may present with both livedo racemosa and stroke are discussed. Finally, we discuss real-life practical issues such as the initial investigations to be performed, long-term follow-up, and therapeutic management of aPL- SS patients.

Background Drug reactions with eosinophilia and systemic symptoms (DRESSs) and acute generalized exanthematous pustulosis (AGEP) are potentially severe cutaneous adverse drug reactions. Objective To describe the clinical findings and sensitization profiles of DRESS and AGEP patients who had been administered iodinated contrast media (ICM). Methods All adult patients in the dermatologist's French Investigators for Skin Adverse Reactions to Drugs (FISARD) network diagnosed with a DRESS or AGEP highly suspected to have been caused by an ICM were included retrospectively. Results Thirteen DRESS patients and 19 AGEP patients who had been administered ICM were included, and the median delay in DRESS and AGEP occurrence after ICM administration was short, 4 and 1 days, respectively. Five AGEP patients had systemic involvement. A high cosensitization rate (46%) was observed among the DRESS patients, mainly with beta-lactam antibiotics. Overall, 77% of our patients were sensitized to several ICM. Patch tests identified the suspected ICM for 21 cases (72%). The retrospective nature, the limited number of subjects, the absence of a control group of healthy individuals, and the lack of detailed information on previous exposure to sensitizing drugs are limitations of this study. Conclusions We report a large series of DRESSs and AGEPs related to ICM administration. Skin tests appear useful for diagnosis and potentially to identify alternative ICM.

International audience; No abstract available

Coronavirus disease 2019 (COVID‐19), a respiratory tract infection caused by a novel human coronavirus, the severe acute respiratory syndrome coronavirus 2, leads to a wide spectrum of clinical manifestations ranging from asymptomatic cases to patients with mild and severe symptoms, with or without pneumonia. Given the huge influence caused by the overwhelming COVID‐19 pandemic affecting over three million people worldwide, a wide spectrum of drugs is considered for the treatment in the concept of repurposing and off‐label use. There is no knowledge about the diagnosis and clinical management of the drug hypersensitivity reactions that can potentially occur during the disease. This review brings togetherall the published information about the diagnosis and management of drug hypersensitivity reactions due to current and candidate off‐label drugs andhighlights relevant recommendations. Furthermore, it gathers all the dermatologic manifestations reported during the disease for guiding the clinicians to establish a better differential diagnosis of drug hypersensitivity reactionsin the course of the disease.

Immune modulation is a key therapeutic tool for allergic diseases and asthma. It can be achieved in an antigen-specific way via allergen immunotherapy (AIT) or in endotype-driven approach using biologicals that target the major pathways of the type 2 (T2) immune response: IgE, IL-5 and IL-4/IL-13. COVID-19 vaccine provides an excellent opportunity to tackle the global pandemics and is currently being applied in an accelerated rhythm worldwide. It works as well through immune modulation. Thus, as there is an obvious interference between these treatment modalities recommendations on how they should be applied in sequence are expected. The European Academy of Allergy and Clinical Immunology (EAACI) gathered an outstanding expert panel under its Research and Outreach Committee (ROC). This expert panel was called to evaluate the evidence and formulate recommendation on the administration of COVID-19 vaccine in patients with allergic diseases and asthma receiving AIT or biologicals. The panel also formulated recommendations for COVID-19 vaccine in association with biologicals targeting the type 1 or type 3 immune response. In formulating recommendations, the panel evaluated the mechanisms of COVID-19 infection, of COVID-19 vaccine, of AIT and of biologicals and considered the data published for other anti-infectious vaccines administered concurrently with AIT or biologicals.

Objectives of the studyDuring the SARS-CoV-2 pandemic, the media has often mentioned the presence of quinine in tonic water. Media accounts of quinine's antiviral effect in vitro, as well as press reports about quinine-based compounds, such as hydroxychloroquine, have sparked renewed public interest in drinking tonic water, which could perhaps result in an increase in allergic phenomena. On the 200th anniversary of the discovery of quinine, our main objective was to analyze hypersensitivity reactions, related to the consumption of beverages containing quinine, described in the literature.Patients and methodsWe analyzed case reports indexed on Pubmed, Scopus, and Google Scholar. A quinine causality score was calculated for each of the observations. A quinine assay was performed on several beverages for which the quinine content had not been published.ResultsIn parallel with related pharmacokinetic studies, these case reports consist of 26 observations. The case reports mainly related to young men, with symptoms of varying severity, mainly dermatological, with fixed drug eruption, generalized rashes, hives; hematological, with thrombocytopenia, hemorrhagic syndrome, thrombotic microangiopathy; more rarely ocular, cardiac or auditory. The level of causality of quinine is certain for three cases, probable for twenty-two, possible for two. The levels of quinine, all conforming to the standards, were lower in the spirits and the cooked wine than those of tonic water.DiscussionPossibly under-diagnosed, the main mechanism of these reactions is immuno-allergic, without any cross-reaction with other quinolines having been shown. In these patients and breastfeeding women of G6PD deficient newborns, any medicines, phytotherapy, homeopathy, or even cosmetics containing quinine, on the basis of a proposed list, should be avoided., Objectifs de l’étudeLa pandémie à SARS-CoV-2 voit nombre de médias relayer la présence de quinine dans les eaux toniques. Si son effet antiviral a été soulevé in vitro, l’amalgame avec ses dérivés, comme l’hydroxychloroquine, suscite un attrait pour ces eaux. Dans le cadre supplémentaire du bicentenaire de la découverte de la quinine, l’objectif principal vise à analyser les réactions d’hypersensibilité liées à la consommation de boissons contenant de la quinine décrites dans la littérature.Patients et méthodesNous avons analysé les cas publiés indexés sur Pubmed, Scopus, Google Scholar. Un score d’imputabilité de la quinine a été calculé pour chacune des observations. Un dosage de quinine a été pratiqué sur plusieurs breuvages dont la vérification de teneur n’avait pas fait l’objet de publication.RésultatsEn parallèle d’études pharmacocinétiques connexes, ce corpus compte 26 observations. Elles concernent principalement des hommes jeunes, dont la gravité des symptômes est variable : essentiellement dermatologique, avec érythème pigmenté fixe, exanthème généralisé, urticaires ; hématologique, avec thrombopénie, syndrome hémorragique, microangiopathie thrombotique ; plus rarement oculaire, cardiaque ou auditive. Le niveau d’imputabilité de la quinine est certain pour trois cas, probable pour vingt-deux, possible pour deux. Les teneurs testées des apéritifs et d’un vin cuit, toutes conformes aux normes, sont moindres que celle des eaux toniques.DiscussionPeut-être sous diagnostiqué, le mécanisme majoritaire est de type immuno-allergique, sans qu’une réaction croisée avec d’autres quinoléines ait pu être montrée. Chez ces patients et les femmes allaitantes de nouveau-nés déficitaires en G6PD, tout médicament, phytothérapie, homéopathie, voire cosmétique contenant de la quinine, sur la base d’une liste didactique proposée, seraient à écarter.

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.

Sophie Seité,1 Charles Taieb,2 Nhân Pham-Thi,3,4 Annick Barbaud5,6 1La Roche-Posay Dermatological Laboratories, Levallois-Perret, France; 2European Market Maintenance Assessment, Fontenay-sous-Bois, France; 3Ecole Polytechnique, Economics, Palaiseau, France; 4Institut Pasteur Paris, Allergology, Paris, France; 5Dermatology and Allergy Department, Tenon Hospital, Medicine Sorbonne University, Paris, France; 6Assistance Publique-Hôpitaux de Paris, Paris, FranceCorrespondence: Sophie Seit&#x00E9La Roche-Posay Dermatological Laboratories, 62 Quai Charles Pasqua, Levallois-Perret, 92300, FranceTel +33 1 49 64 33 40Email sophie.seite@loreal.comBackground: Increased allergy frequency may have a significant impact on the skin, one of the largest targeted organs for allergic and immunological responses.Methods: An online survey of 2036 adults as a representative sample of the French general population was conducted to evaluate the prevalence of self-reported allergies, the populations who report allergies and the skin conditions related to allergies.Results: In general, 20.2% of French adults (average age 45 ± 15.8 years) reported allergies. These allergies were respiratory allergies (55.3%), skin allergies (48.8%) and food allergies (27.9%), and 78.9% indicated that their reported allergies were diagnosed by a doctor. In addition, 53.2% of individuals reporting an allergy also indicated that they experienced associated skin reactions. In comparison to those who did not report an allergy, these individuals were 1.5 to 4 times more likely to have a skin disease and 3 times more likely to have sensitive skin or skin reactions when using skincare products.Conclusion: It is estimated that over 10 million French adults have allergies. These data will help increase awareness among the allergic population and healthcare professionals about the burden associated with allergies and the need for management to reduce their health impact.Keywords: allergies, food allergy, skin allergy, respiratory allergy, prevalence, skin side effects

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.

Immediate and non-immediate hypersensitivity reactions to iodinated contrast media (ICM) have been reported to occur in a frequency of about 0.5-3% of patients receiving non-ionic ICM. The diagnosis and management of these patients varies among guidelines published by various national and international scientific societies, with recommendations ranging from avoidance or premedication to drug provocation test. This position paper aims to give recommendations for the management of patients with ICM hypersensitivity reactions and analyze controversies in this area. Skin tests are recommended as the initial step for diagnosing patients with immediate and non-immediate hypersensitivity reactions; besides, they may also help guide on tolerability of alternatives. Reexposition or drug provocation test should only be done with skin test-negative ICMs.The decision for performing either reexposition or drug provocation test needs to be taken based on a risk-benefit analysis. The role of in vitro tests for diagnosis and pretreatment for preventing reactions remains controversial.

Resume Introduction Le lymphome intravasculaire a grandes cellules B (LIVB) est une hemopathie rare de diagnostic difficile. La biopsie cutanee en peau saine pourrait etre utile pour en faire le diagnostic. Nous rapportons un cas de LIVB diagnostique grâce a cet examen, et proposons une revue de la litterature afin d’en preciser la sensibilite. Observation Une femme de 67 ans etait hospitalisee pour fievre prolongee inexpliquee (FPI) et alteration de l’etat general. Le bilan biologique montrait un syndrome inflammatoire, une elevation des LDH superieure a 2000 UI/L, une cytolyse hepatique et un abaissement du temps de prothrombine a 47 %. Les prelevements infectieux et les examens d’imagerie eliminaient une etiologie infectieuse ou inflammatoire, ainsi qu’une neoplasie solide. Une biopsie cutanee en peau saine permettait de retenir le diagnostic de LIVB. Discussion Ce cas clinique illustre l’interet de la biopsie cutanee en peau saine pour le diagnostic de LIVB chez les patients hospitalises pour FPI. A partir d’une revue systematique de la litterature dans PubMed/Medline, nous avons inclus huit series d’au moins trois patients evaluant l’interet de la biopsie cutanee en peau saine pour le diagnostic de LIVB. La sensibilite pour le diagnostic variait de 67 % a 100 %, avec une sensibilite de 100 % dans quatre des huit etudes. Le detail des sites de biopsie etait disponible dans trois etudes et la sensibilite etait globalement similaire entre la cuisse, l’abdomen et les bras. Conclusion La biopsie cutanee en peau saine realisee sur au moins deux sites est un examen sensible et peu invasif pour le diagnostic precoce de LIVB.

Resume Introduction Les necroses des doigts sont rares en comparaison de celles des membres inferieurs. Elles sont une urgence medico-chirurgicale. Un bilan etiologique approfondi est indispensable. La maladie des agglutinines froides est une cause rare de necroses digitales, de diagnostic difficile et souvent non recherchee. Observation Nous rapportons le cas d’un homme de 57 ans qui presentait un phenomene de Raynaud de la main gauche d’apparition recente, complique secondairement de necroses digitales survenues apres exposition professionnelle au froid (conducteur d’un chariot de manutention). Le bilan etiologique permettait de poser le diagnostic de maladie des agglutinines froides idiopathique. Un traitement par rituximab et des soins locaux ont permis une cicatrisation complete. Discussion La maladie des agglutinines froides est une cause rare d’anemie hemolytique auto-immune. Les signes cliniques cutanes, paroxystiques, declenches par le froid, sont au premier plan. Il existe une forme idiopathique et une forme secondaire a une hemopathie lymphoide chronique, une maladie auto-immune ou une infection ; un bilan etiologique est indispensable. Le traitement qui permet d’obtenir le meilleur taux de reponse, associe a une bonne tolerance, est a ce jour le rituximab en perfusions hebdomadaires pendant 1 mois.

International audience; Coronavirus disease 2019 (COVID-19), a respiratory tract infection caused by a novel human coronavirus, the severe acute respiratory syndrome coronavirus 2, leads to a wide spectrum of clinical manifestations ranging from asymptomatic cases to patients with mild and severe symptoms, with or without pneumonia. Given the huge influence caused by the overwhelming COVID-19 pandemic affecting over three million people worldwide, a wide spectrum of drugs is considered for the treatment in the concept of repurposing and off-label use. There is no knowledge about the diagnosis and clinical management of the drug hypersensitivity reactions that can potentially occur during the disease. This review brings together all the published information about the diagnosis and management of drug hypersensitivity reactions due to current and candidate off-label drugs and highlights relevant recommendations. Furthermore, it gathers all the dermatologic manifestations reported during the disease for guiding the clinicians to establish a better differential diagnosis of drug hypersensitivity reactions in the course of the disease.

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.

Purpose of review Protein contact dermatitis (PCD) is a chronic eczema because of immediate hypersensitivity to protein and not related to haptens. As it has to be diagnosed by prick tests, it is probably under-recorded and under-estimated that is why it is important for dermatologists, allergists and occupational physicians to better know this peculiar contact dermatitis. Recent findings Some recent series have emphasized that PCD is mainly an occupational dermatosis, mainly observed in food handlers. Summary PCD is a chronic eczematous dermatitis, possibly exacerbated by work, suggested if associated with inflammatory perionyxis (paronychial inflammation) and immediate erythema with pruritis, to be investigated when the patient resumes work after a period of interruption. Prick tests with the suspected protein-containing material are essential, as patch tests have in most of the cases negative results. Prick-by-prick tests with fresh material are recommended. The product has to be 'pricked', for instance the food, and immediately after the forearm is pricked. In case of multisensitization revealed by prick tests, it is advisable to analyse IgE against recombinant allergens. History of atopy found in 56--68% of the patients has to be checked for. Most of the cases are observed among food-handlers but PCD can also be because of nonedible plants, latex, hydrolyzed proteins or animal proteins.

Arzneimittelüberempfindlichkeit – Hautmanifestationen – Klassifikation – Nomenklatur – Anaphylaxie – Exanthem – Positionspapier

International audience; A recent survey of the European Academy of Allergy and Clinical Immunology (EAACI) Drug Allergy Interest Group (DAIG) on how European allergy specialists deal with beta-lactam (BL) hypersensitivity demonstrated a significant heterogeneity in current practice, suggesting the need to review and update existing EAACI guidelines in order to make the diagnostic procedures as safe and accurate, but also as cost-effective, as possible. For this purpose, a bibliographic search on large studies regarding BL hypersensitivity diagnosis was performed by an EAACI task force, which reviewed and evaluated the literature data using the GRADE system for quality of evidence and strength of recommendation. The updated guidelines provide a risk stratification in BL hypersensitivity according to index reaction(s), as well as an algorithmic approach, based on cross-reactivity studies, in patients with a suspicion of BL hypersensitivity and an immediate need for antibiotic therapy, when referral to an allergist is not feasible. Furthermore, the update addresses availability and concentrations of skin test (ST) reagents, ST and drug provocation test (DPT) protocols, as well as diagnostic algorithms and administration of alternative BL in allergic subjects. Specifically, distinct diagnostic algorithms are suggested depending on risk stratification of the patient into high and low risk based on the morphology and chronology of the reaction, immediate (i.e., occurring within 1 to 6 hours after the last administered dose) or nonimmediate (i.e., occurring more than 1 hour after the initial drug administration), and the reaction severity. Regarding the allergy workup, the main novelty of this document is the fact that in some low-risk nonimmediate reactions ST are not mandatory, especially in children. For DPT, further studies are necessary to provide data supporting the standardization of protocols, especially of those regarding nonimmediate reactions, for which there is currently no consensus.

Aims Sneddon’s syndrome (SS) may be classified as antiphospholipid positive (aPL+) or negative (aPL− SS). An association between Libman–Sacks (LS) endocarditis and strokes has been described in aPL+ patients. To describe cardiac involvement in aPL− SS and assess the potential association between LS endocarditis and severity or recurrence of neurological symptoms. Methods and results This longitudinal cohort study included aPL− SS patients followed in our departments between 1991 and June 2018. All patients underwent transthoracic 2D and Doppler echocardiography at diagnosis. Follow-up echocardiography was performed annually and the potential relationship between LS endocarditis development and neurovascular relapse as well as long-term cardiac worsening was prospectively assessed. We included 61 patients [52 women; median age 45 (range 24–60)]. For valvular involvement, 36 (59%) patients showed leaflet thickening; 18 (29.5%) had LS endocarditis at baseline. During a median follow-up of 72 months, LS endocarditis developed in eight (17.4%) patients, and 13 (28.3%) showed significant worsening of their cardiac status, including two who needed valvular replacement. After adjusting for baseline antithrombotic treatment regimen, neither the presence of LS endocarditis at baseline nor development during follow-up was associated with neurological relapse [hazard ratio (HR): 1.06, 95% confidence interval (CI): 0.33–4.74, P = 0.92] and [HR: 0.38, 95% CI: 0.02–1.89, P = 0.31], respectively. Conclusion A long-term follow-up is needed to detect cardiac complications in aPL− SS. No change in neurological relapse was observed in patients presenting LS endocarditis occurrence during follow-up without any modification in antithrombotic treatment. Further research is necessary to assess the usefulness of treatment escalation in these patients.

Symmetrical drug-related intertriginous and flexural exanthema is a flexural eruption that occurs within a few days of drug exposure. Antibiotics and iodinated contrast agents are the most frequent triggers. Skin testing has low sensitivity. Rechallenge identifies the culprit drug without serious manifestations. The symmetrical drug-related intertriginous and flexural ex-anthema (SDRIFE) is a delayed flexural exanthema induced by a systemic drug without previous cutaneous sensitization, typically presenting as "a sharply defined symmetrical erythema of the gluteal area and in the flexural or intertriginous folds without systemic symptoms and signs." 1 SDRIFE clinically resembles Baboon syndrome (BS); however, in BS, patients develop the exanthem after systemic exposure to an allergen to which they have been previously topically sensitized. 2 We retrospectively reviewed records from 2 French dermatology departments between 2006 and 2018 for adults with SDRIFE as defined by Hausermann et al 1 : (1) exposure to systemically administered drug either following the first or subsequent dose, (2) sharply demarcated erythema of the gluteal and/or inguinal area, (3) involvement of at least 1 other flexural localization, (4) symmetry of affected area, and (5) absence of systemic symptoms and signs. Twelve patients were excluded because of previous topical sensitization to the allergen (BS, n ¼ 2), diffuse maculopapular rash (MPR) with flexural reinforcement (n ¼ 7), other causes of flexural rash, for example, acute generalized exanthematous pustulosis (AGEP), toxic er-ythema due to chemotherapy (TEC) based on clinical and histological findings (n ¼ 2), and flexural erythema thought to be drug-induced but without relapse after reexposure (n ¼ 1). Patch tests (PTs) (IQ ultrachambers, Chemotechnique Diagnostics, Velinge, Sweden), skin prick tests (SPTs), and intradermal tests (IDTs) with delayed readings were performed following European guidelines 3 (Table I). We further reviewed all published cases of SDRIFE since Hausermann et al's publication (2004-2018). Eighteen patients were included, 10 females and 8 males, with mean and median ages of 57 years (range, 33-83 years). Erythematous patches or plaques affecting a mean of 5 (range, 2-7) large or small skin folds (especially inguinal, gluteal, axillary, and mammary) (Figure 1, Table I) were observed. Four patients had localized skin vesicles or bullae and 1 (no. 16) had mucosal involvement. The eruption occurred shortly after drug exposure (median, 22 hours; mean, 34; range, 0.5-120). The causative drug was discontinued immediately in all patients, 10 were treated with topical steroids, and resolution of lesions was observed within a median of 4 days (mean, 6.2; range, 1-18). Lymphopenia was found in 6 of 12 patients (50%; range, 350-1400/mm 3), not explained by a distinct underlying condition. The most frequent histological pattern, found in 5 of 11 patients who had a skin biopsy, was subepidermal edema with a polymorphous perivascular and interstitial infiltrate of neutro-phils, eosinophils, and lymphocytes in the upper dermis. Four patients had a spongiotic and/or lichenoid pattern on skin biopsy and 2 had a nonspecific scant lymphocytic superficial peri-vascular infiltrate. There was no obvious relationship between histology and the clinical presentation and severity of the rash or timing of skin biopsy. The suspected drug was an antibiotic in 10 of 18 cases (56%), including amoxicillin AE clavulanate in 4 (22%), a iodinated contrast agent (ICA) in 5 of 18 (28%), an analgesic in 2 of 18, and fluconazole in 1 of 18 (Table I). Fourteen patients had PT, 12 had SPT, and 11 IDT with delayed readings. Testing was performed within 1 month to 9 years of the original reaction, and most patients (13 of 16) were tested within 1 year of the reaction. Positive skin test results were obtained only in 5 patients, all with antibiotics: PT in 3 of 14 cases (21%): 1 with amoxicillin-clavulanate and 2 with pristinamycin; IDT in 2 of 11 cases (18%) with amoxicillin AE clavulanate. Skin test results remained negative in patient number 2 who also had a SDRIFE due to amoxicillin confirmed by rechallenge test (RT). Results of all skin tests performed with ICAs (PT n ¼ 3, SPT and IDT n ¼ 5) were negative. The result of RT with the suspected causative drug, performed in 9 patients with negative skin test results, was always positive, without severe cutaneous or systemic manifestations. There was no obvious relationship between clinical presentation and positivity of skin test results. The median time for SDRIFE recurrence after reexposure to the drug (induced by RT [n ¼ 9] or skin tests [n ¼ 1]) was 12 hours (mean, 15 hours; range 2.5-30), shorter than during the first episode. SDRIFE is thought to involve a type IV delayed-hypersensitivity immune response, because it occurs within a few hours to a few days after drug exposure, and there is evidence for a T-cellemediated reaction, 1,4 though the precise physiopa-thology is not known. Antibiotics are common triggering agents in the literature (60% in Hausermann et al's 1 review, 33% in our literature review [2004-2018], n ¼ 51 [see Tables E1 and E2 in this article's Online Repository at www.jaci-inpractice.org]), especially beta-lactams (55% in Hausermann et al's review and 23% in our review), but only 5 cases of SDRIFE due to ICAs were reported. 5 In previously published cases, skin test results were positive more frequently than in our study, 40% of PTs, 11% of SPTs, and 70% of IDTs, for various drugs (antibiotics and others), possibly due to a publication bias. Different methods for identifying the culprit drug might be necessary in SDRIFE. Skin testing on affected sites is one option; however, 3185

International audience

Resume Introduction L’incidence des cancers est augmentee chez les patients atteints de sclerodermie systemique (ScS). De plus, des etudes recentes ont mis en evidence que la presence d’anticorps anti-ARN polymerase III etait associee a un risque de cancer plus eleve chez les patients atteints de ScS. Observations Nous presentons les cas de deux hommes de 56 et 23 ans atteints de sclerodermie systemique, sans anticorps anti-Scl70 ni anti-centromere, ayant des anticorps anti-ARN polymerase III. Dans les deux cas, un diagnostic de cancer de la sphere oro-pharyngee a ete pose apres realisation d’examens complementaires demandes devant des signes cliniques d’orientation. Discussion Ces observations illustrent le fait que les anticorps anti-ARN polymerase III ont un interet diagnostique lors de la ScS et que leur presence doit faire rechercher un cancer associe (meme en l’absence de signes cliniques d’orientation).

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.

Resume But Les reactions d’hypersensibilite (HS) aux sels de platine (SP) et aux taxanes (TX) sont frequentes. L’objectif de notre etude etait d’evaluer l’interet des tests cutanes et des inductions de tolerance aux SP et TX. Methodes Il s’agit d’une etude retrospective realisee entre janvier 2007 et fevrier 2016, incluant les patients adresses pour suspicion d’HS immediate ou retardee. Les tests cutanes, prick tests (pT) et intradermoreaction (IDR), etaient realises selon les recommandations de l’ENDA/EAACI et les inductions de tolerance (IT) selon un protocole en 12 paliers. Resultats Chez les 99 patients inclus (30 hommes, 69 femmes, âge moyen 60,4 ans), les SP etaient suspectes chez 86 et les TX chez 13. Les tests cutanes etaient positifs chez 25 patients (7 pT et 18 IDR), 23 avec les SP et 2 avec les TX. Une IT etait proposee chez 50 patients, realisee chez 33 (30 avec SP et 3 avec TX), bien supportee chez 29, necessitant une adaptation chez 7 mais echouait chez 4 patients. Chez ces 4 derniers, les tests cutanes etaient positifs. Parmi les patients ayant des tests positifs a l’oxaliplatine, 75 % avaient une reaction d’HS lors de l’IT, soit une proportion deux fois plus grande que parmi les patients ayant des tests cutanes negatifs. Des reactions croisees survenaient dans 2 % des cas avec les SP et 7 % avec les TX. Conclusion Cette experience francaise confirme l’interet des IT en 12 etapes, permettant dans la plupart des cas de poursuivre une chimiotherapie chez un patient avec HS. Les tests cutanes sont utiles pour l’etude des reactions croisees, cependant leur realisation doit etre consideree au cas par cas.

SummaryBackground 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.

Resume Buts Evaluer la couverture vaccinale de patients atteints de psoriasis, avant l’instauration d’un traitement immunosuppresseur ou son changement pour un autre, et verifier la realisation des vaccins prescrits. Materiels et methodes Il s’agit d’une etude observationnelle, transversale, bicentrique, menee sur neuf mois. Les patients atteints de psoriasis avec indication a un traitement immunosuppresseur (ciclosporine, methotrexate, etanercept, infliximab, adalimumab, ustekinumab) ont ete inclus. Un questionnaire permettait d’evaluer les antecedents, les traitements anterieurs, le statut vaccinal, les resultats des serologies virales (hepatite B, rougeole, varicelle) et les motifs de non-vaccination. Resultats Sur 68 patients inclus, un tiers ont rapporte le carnet de vaccination. Les patients ayant deja recu un traitement immunosuppresseur representaient 54,4 % de l’effectif ; seuls 9 etaient a jour du vaccin contre la grippe et 3 contre le pneumocoque. Un seul patient etait a jour pour l’ensemble des vaccins recommandes. La serologie d’hepatite B etait negative dans 61 % des cas. Les vaccins suivants ont ete mis a jour : DTP (2), DTPCoqueluche (12), grippe (22), pneumocoque (45) et hepatite B (6). Aucun des 3 patients ayant un projet de voyage en zone d’endemie de fievre jaune n’a ete vaccine. Cinquante-trois patients (78 %) declaraient avoir deja eu la varicelle et 43 (63,2 %) avoir eu une des trois maladies (rougeole, rubeole ou oreillons). La serologie varicelle realisee chez 52 des 68 patients montrait 98 % de sujets immunises. Les motifs les plus frequents de statut vaccinal non a jour etaient l’absence d’information ou de proposition par le medecin traitant et l’oubli. Conclusion Cette etude a permis de sensibiliser les patients et les professionnels de sante sur les nouvelles recommandations vaccinales dans une population particulierement exposee au risque infectieux.

International audience

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.

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.

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: 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.

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.

Drug hypersensitivity reactions (DHRs) are common, and the skin is by far the most frequently involved organ with a broad spectrum of reaction types. The diagnosis of cutaneous DHRs (CDHR) may be difficult because of multiple differential diagnoses. A correct classification is important for the correct diagnosis and management. With these guidelines, we aim to give precise definitions and provide the background needed for doctors to correctly classify CDHR.

International audience; Controversies exist with regard to in vivo approaches to delayed immunologically mediated adverse drug reactions, such as exanthem (maculopapular eruption), drug reaction with eosinophilia and systemic symptoms, acute generalized exanthematous pustulosis, Stevens-Johnson syndrome/toxic epidermal necrolysis, and fixed drug eruptions. In particular, widespread differences exist between regions and practice on the availability and use of intradermal and patch testing, the standard drug concentrations used, the use of additional drugs in intradermal and patch testing to help determine cross-reactivity, the timing of testing in relation to the occurrence of the adverse drug reaction, the use of testing in specific phenotypes, and the use of oral challenge in conjunction with delayed intradermal and patch testing to ascertain drug tolerance. It was noted that there have been advances in the science of delayed T cell-mediated reactions that have shed light on immunopathogenesis and provided a mechanism of preprescription screening in the case of HLA-B*57:01 and abacavir hypersensitivity and HLA-B*15:02 and carbamazepine Stevens-Johnson syndrome/toxic epidermal necrolysis in Southeast Asian subjects. Future directions should include the collaboration of large international networks to develop and standardize in vivo diagnostic approaches, such as skin testing and patch testing, combined with ex vivo and in vitro laboratory approaches.

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.