Most chilblains observed during the COVID-19 outbreak occur in patients who are negative for COVID-19 on polymerase chain reaction and serology testing.

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

Cross-reactivity in beta-lactams after a non-immediate cutaneous adverse reaction: experience of a reference centre for toxic bullous diseases and severe cutaneous adverse reactions.

BACKGROUND: Cross-reactivity among beta-lactam antibiotics (BL) is essentially reported in immediate hypersensitivity. OBJECTIVES: To evaluate cross-reactivity beyond BLs in patients with non-immediate cutaneous adverse drug reaction (non-immediate CADR) managed in a dermatology reference centre of toxic bullous and severe CADRs. PATIENTS/MATERIALS/METHODS: We conducted a retrospective single-centre study in consecutive patients consulting between 2010 and 2018 with an active BL-suspected non-immediate CADR and explored by cutaneous tests [patch tests (PT) and intradermal tests (P-IDR)] for at least three penicillin's subclasses and amino- and non-amino-cephalosporins (at least one aminocephalosporin). Cross-reactivity among subclasses was investigated for patients with positive tests. RESULTS: We included 56 patients, among whom 46 amoxicillin-suspected were and seven cephalosporin-suspected. Twenty-nine had severe CADR, and 27 had non-immediate maculopapular exanthema (MPE). Twenty-two had positive tests (18 for AS and four for CS). Among the 18 positive amoxicillin-suspected, 10 (55.6%) showed cross-reactivity with one or more other BL: 9 (50%) with another penicillin and 3 (16.5%) with a non-aminocephalosporin. No amoxicillin- or cephalosporin-suspected patient showed cross-reactivity with aztreonam or carbapenems. P-IDR showed cross-reactivity only once. CONCLUSION: After a suspected BL-induced non-immediate CADR, a large allergologic exploration is needed to confirm the diagnosis and evaluate cross-reactivity. In our population including cases of severe CADRs and MPE with late delay of onset, cross-reactivity was frequent and PT was sufficient to this purpose. The frequent cross-reactivity among penicillins encourages stopping this whole family and to test cephalosporins, aztreonam and carbapenems for which cross-allergies are rarer.

Cutaneous adverse drug reaction to oral acetazolamide and skin tests.

BACKGROUND: Few cases of cutaneous adverse drug reactions (CADR) to oral acetazolamide, a non-antimicrobial sulfonamide, have been previously reported, and the interest of acetazolamide skin tests has never been studied. OBJECTIVES: We report a series of ten patients with oral acetazolamide CADR and skin tests. PATIENTS AND METHODS: The files of ten patients with CADR secondary to oral acetazolamide prescribed for cataract surgery in most cases referred between 2001 and 2011 in four French dermatology and allergy departments were retrospectively reviewed. Skin tests with acetazolamide were performed in nine patients and twelve controls. Other sulfonamides were tested in five of ten patients. RESULTS: Seven patients developed maculopapular exanthema and four had acute generalized exanthematous pustulosis. Patch tests were positive for 8/9 patients, prick tests for 2/4 and intradermal tests for 3/3. Patch and prick or intradermal test results were concordant in 2/3 positive subjects. Patch tests for other sulfonamides were negative, as were patch tests in controls. CONCLUSIONS: We report the largest series of CADR to oral acetazolamide (maculopapular exanthema or acute generalized exanthematous pustulosis). A drug eruption after cataract surgery should be investigated for accountability of acetazolamide. In view of this retrospective study, skin tests and particularly intradermal tests appear to be an important contribution to demonstrate accountability.

A multicentre study to determine the value and safety of drug patch tests for the three main classes of severe cutaneous adverse drug reactions.

BACKGROUND: Drug patch tests (PTs) can reproduce delayed hypersensitivity to drugs and entail a moderate re-exposure of patients to offending drugs. OBJECTIVES: To determine the value of PTs for identifying the responsible drug in severe cutaneous adverse drug reactions (SCARs) such as acute generalized exanthematous pustulosis (AGEP), drug reaction with eosinophilia and systemic symptoms (DRESS) and Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). METHODS: In a multicentre study, PTs were conducted on patients referred for DRESS, AGEP or SJS/TEN within 1 year of their SCAR. All drugs administered in the 2 months prior to and the week following the onset of the SCAR were tested. RESULTS: Among the 134 patients included (48 male, 86 female; mean age 51·7 years), positive drug PTs were obtained for 24 different drugs. These included positive tests for 64% (46/72) of patients with DRESS, 58% (26/45) of those with AGEP and 24% (4/17) of those with SJS/TEN, with only one relapse of AGEP. The value of PTs depended on the type of drug and the type of SCAR (e.g. carbamazepine was positive in 11/13 DRESS cases but none of the five SJS/TEN cases). PTs were frequently positive for beta lactams (22 cases), pristinamycin (11 cases) and in DRESS with pump proton inhibitors (five cases), but were usually negative for allopurinol and salazopyrin. Of 18 patients with DRESS, eight had virus reactivation and positive PTs. In DRESS, multiple drug reactivity was frequent (18% of cases), with patients remaining sensitized many years later. CONCLUSIONS: PTs are useful and safe for identifying agents inducing SCAR.

[Occupational dermatitis in cleaning and maintenance workers. Analysis of 769 cases declared to the Caisse Nationale d'Assurance Maladie des Travailleurs Salariés between 2004 and 2007]. / Les eczémas professionnels chez les travailleurs du secteur du nettoyage et de l'entretien. Étude de 769 déclarations à la Caisse nationale d'assurance maladie des travailleurs salariés entre 2004 et 2007.

BACKGROUND: Employees active in the cleaning and maintenance industry (CMI) are particularly exposed to occupational eczema (OE), which affects the hands in 80 to 90% of cases. This risk of OCE in France was evaluated using data collected by the Occupational Risks Division of the French National Health Insurance Fund for Salaried Workers (CNAMTS). PATIENTS AND METHODS: All cases of OE among CMI employees declared to and recognized by the CNAMTS between 1st January 2004 and 31st December 2007 were selected. The following parameters were noted in each case: age, gender, trade in question, National Health Insurance Office of residence, causal agent and number of days of sick leave. The incidence per 100,000 employees could be determined from the total number of employees followed up by occupational medicine and the numbers working in the CMI. RESULTS: For the 4 years studied, 769 cases of OE were reported in CMI workers representing 2.6% of the salaried employee population. The annual incidence of OE was 43.5 per 100,000 employees. There was a marked female predominance (75.7%). OE led to loss of 32,714 workdays. CONCLUSION: This is the first study conducted in France about OE among NIS employees. It highlights the socioeconomic impact of OE. The difficulties of interpretation show the limits of recognition of occupational disease. Analysis of cases of OE in France and monitoring require the development of a specific database to clarify risk situations and identify priority regional and national preventive actions.

Occupational contact dermatitis in 10,582 French patients reported between 2004 and 2007: a descriptive study.

BACKGROUND: Limited epidemiological data are available in France for occupational contact dermatitis (OCD), a non- infectious inflammatory skin condition arising from direct skin contact with substances used in the workplace. OBJECTIVE: To estimate the occurrence of, and number of workdays lost to, OCD in France. METHODS: Descriptive study of all OCD declared by salaried workers and recognised as occupational disease in France over a 4-year period. RESULTS: 10,582 OCD cases were reported, representing 9.6% of all occupational diseases recognised. The estimated annual incidence of OCD recognised was 15.72/100,000 salaried workers (i.e. 146.87/100,000 employees for all occupational diseases). OCD cases were mainly in the construction and public works industries with 3,057 (36.7%) salaried workers affected. In the services sector, OCD predominantly affected employees aged less than 30 years (41%), particularly hairdressers (69%). OCD accounted for the loss of 395,069 working days. CONCLUSION: OCD represents a significant public health problem in France, particularly for construction workers and hairdressers.

[Management of drug reaction with eosinophilia and systemic symptoms (DRESS)]. / Prise en charge du drug reaction with eosinophilia and systemic symptoms (DRESS).

OBJECTIVE: The management of drug-induced hypersensitivity syndrome or drug reaction with eosinophilia and systemic symptoms (DRESS) is not codified. Demonstration of the reactivation of Herpesviruses illustrates the specific pathophysiology of this syndrome. Proposals for the management of DRESS were elaborated by the cutaneous adverse drug reaction working group of the French Society of Dermatology to help with its management. METHODS: From a review of literature and the experience of the members of this group, consensual proposals were written about diagnostic criteria, tests, treatment options, and follow-up. These proposals will need to be validated in prospective studies. RESULTS: A decisional tree of treatment options is proposed, based on the severity of visceral manifestations. The importance of a rapid withdrawal of the culprit drug and of a long-term follow-up is underlined. Treatment will be adapted to the clinicobiological status (topical corticosteroid, systemic corticosteroid, intravenous gammaglobulins, antivirals).

[Contact allergy to antiseptics: 75 cases analyzed by the dermato-allergovigilance network (Revidal)]. / Allergie de contact aux antiseptiques: 75 cas analysés par le réseau Revidal de dermato-allergovigilance.

AIM: To determine the clinical features of contact dermatitis caused by antiseptics and to ascertain whether the substance responsible is the antiseptic itself or the excipients. PATIENTS AND METHODS: A multicenter, retrospective study based on analysis of all cases reported over a 2-year period to the Dermato-Allergology Vigilance network known as Revidal. Each dossier contained details of the clinical characteristics of lesions, the incriminated antiseptic, the mode of exposure and the results of patch tests done with the antiseptic in question. RESULTS: 75 patients (mean age: 44 years) were sensitized to chlorhexidine (14 cases), hexamidine (20 cases), povidone iodine (14 cases), mercuric antiseptics (3 cases), triclocarban (Septivon, 17 cases), hexamidine-chlorhexidine-chlorocresol (Cytéal, 4 cases), or chlorhexidine surfactant (Hibiscrub), cetrimide or chlorhexidine digluconate (Diaseptyl) (1 case each). Exposure was therapy-related (68 cases), work-related (6 cases; 5 in health workers and 1 in a cattle farmer due to povidone-iodine) or related to cosmetics (1 case, hexamidine). The clinical features consisted mainly of localized contact dermatitis, although generalized eczema occurred in 9 cases due to hexamidine contact. Sensitization was due to the antiseptic itself (53 cases) or to the excipients alone (22 cases), particularly in the 17 cases caused by Septivon. In 27/75 cases (35%), patients exhibited polysensitization to antiseptics belonging to different chemical classes or to other topical drugs. CONCLUSION: Sensitization to antiseptics is probably not rare, with various sources of exposure being present in everyday life. Patch tests are essential for diagnosis in order to distinguish between antiseptic-related and excipient-related sensitization and to screen for polysensitization to topical drugs.

[Acute generalized exanthematous pustulosis induced by drugs with low-digestive absorption: acarbose and nystatin]. / Pustulose exanthématique aiguë généralisée induite par des médicaments à faible absorption intestinale: l'acarbose et la nystatine.

INTRODUCTION: Acarbose and nystatin are usually well-tolerated drugs because of their minimal intestinal absorption. We report herein two cases of acute generalized exanthematous pustulosis induced by these two molecules. CASES REPORT: A 43 year-old man with a history of insulin-deficient diabetes was admitted to our department for a febrile generalized cutaneous pustular erythema, that had appeared 48 hours after acarbose (Glucor) introduction. Acarbose was discontinued and the eruption resolved in one week. A 29 year-old man developed a flexural erythema twenty four hours after nystatin (Mycostatin) treatment, progressing towards a febrile pustular erythroderma, with elevated neutrophilic and eosinophilic counts. The lesions regressed rapidly with topical steroid treatment. The patch tests performed a few months later with Mycostatin and nystatin were positive. DISCUSSION: The clinical presentation of these two patients was typical of acute generalized exanthematous pustulosis, according to the EuroSCAR group criteria and acarbose and nystatin were the most likely factors that caused the disease according to the French unexpected or toxic drug reaction assessment. The minimal intestinal absorption of these two molecules explains their usual good tolerance. However, some cases of toxiderma have already been reported. There is the first described case of acute generalized exanthematous pustulosis with acarbose. Our two observations underline the possibility of severe toxiderma induced by low-absorbed and low-blood concentration molecules and focus on the need to take them in account in the toxiderma anamnesis.

Clinicopathologic correlation in erythema multiforme and Stevens-Johnson syndrome.

BACKGROUND AND DESIGN: To confirm the recent hypothesis that the spectrum of severe erythema multiforme (EM) is actually composed of two different disorders, we retrospectively studied 38 such cases, particularly in regard to their histopathologic features. Based on photographs and a recent proposal, the cases were classified as EM major when the eruption consisted of typical or raised atypical target lesions located on the extremities and/or the face or as Stevens-Johnson syndrome when the eruption consisted of flat atypical target lesions or purpuric macules that were widespread or distributed on the trunk. The cases were also assessed for causal agent. A biopsy specimen was obtained in each case. Several histologic parameters were analyzed (and scored) without clinical data and correlated to the clinical pattern. These parameters were first studied in a global assessment and then in a detailed evaluation. RESULTS: The global assessment showed two different histological patterns: (1) a predominantly inflammatory pattern characterized by a lichenoid infiltrate and epidermal necrosis that mainly affected the basal layer; and (2) a predominantly necrotic pattern in which major epidermal necrosis and minimal inflammatory infiltration were found. The former pattern was associated with EM major, the latter with Stevens-Johnson syndrome (P < .001) and with drug-related cause (P < .001). The detailed evaluation showed also less epidermal necrosis, and more dermal inflammation, and more exocytosis in EM major. Conversely, there was more epidermal necrosis, less dermal inflammation, and less exocytosis in Stevens-Johnson syndrome. The difference was statistically significant for the inflammation and exocytosis. CONCLUSIONS: This study suggests that the two different symptomatologies in the spectrum of severe EM correlate with two different patterns of histopathologic changes. A prospective multicentered study should be conducted to definitively characterize these entities.