[Polymorphism and differential diagnosis of neonatal lupus erythematosus]. / Polymorphisme et diagnostics différentiels du lupus érythémateux néonatal.

INTRODUCTION: Neonatal lupus erythematosus (NEL) is a rare condition secondary to transplacental transfer of maternal anti-nuclear antibodies, generally anti-Ro/SSA. The most common signs are dermatological and cardiac. The most frequently reported clinical association is periorbital erythema, known as "owl eye", and bipolar erythematous maculopapular plaques with fine scales. However, many semiological variants can result in diagnostic errors or delays. PATIENTS AND METHODS: This was a single-centre retrospective observational study collating all cases of NEL seen at paediatric dermatology consultations between 2010 and 2018. The diagnosis of NEL was confirmed by the presence of specific antinuclear antibodies (ANA) in the mother. The aim was to describe the different clinical forms of NEL and to discuss differential diagnosis. RESULTS AND DISCUSSION: We identified ten cases of NEL, all addressed without diagnosis or with misdiagnosis. They were divided into 3 groups based on the semiology of skin lesions: 5 presented inflammatory macular papules on the cephalic extremity and head; 3 presented acquired periorbital depigmentation; 2 presented atrophic and diffuse livedoid lesions. None had heart disease and associated haematological and hepatic damage was mild. Spontaneous remission was seen in all cases before the age of 6 months. The mothers, who were generally symptom-free or paucisymptomatic, presented anti-Ro/SSA NAAs. CONCLUSION: Recognition of the different clinical forms of NEL enables early institution of suitable therapy and monitoring of subsequent pregnancies.

Sensitivity, specificity, and accuracy of molecular profiling on circulating cell-free DNA in refractory or relapsed multiple myeloma patients, results of MM-EP1 study.

As a promising alternative to bone marrow aspiration (BMA), mutational profiling on blood-derived circulating cell-free tumor DNA (cfDNA) is a harmless and simple technique to monitor molecular response and treatment resistance of patients with refractory/relapsed multiple myeloma (R/R MM). We evaluated the sensitivity and specificity of cfDNA compared to BMA CD138 positive myeloma plasma cells (PCs) in a series of 45 R/R MM patients using the 29-gene targeted panel (AmpliSeq) NGS. KRAS, NRAS, FAM46C, DIS3, and TP53 were the most frequently mutated genes. The average sensitivity and specificity of cfDNA detection were 65% and 97%, respectively. The concordance per gene between the two samples was good to excellent according to Cohen's κ coefficients interpretation. An increased number of mutations detected in cfDNA were associated with a decreased overall survival. In conclusion, we demonstrated cfDNA NGS analysis feasibility and accuracy in R/R MM patients who may benefit from early phase clinical trial.

Clinical characteristics of molluscum contagiosum in children in a private dermatology practice in the greater Paris area, France: a prospective study in 661 patients.

BACKGROUND: Series regarding the clinical characteristics of molluscum contagiosum (MC) are retrospective and concern small defined populations seen in a hospital setting. METHODS: We prospectively studied patients under 15 years of age with MC seen in 25 private dermatology practices in the greater Paris area during 1 year. RESULTS: Six hundred fifty patients were included. The mean age was 6 years. Of the patients, 30.5% had had MC in the past, 53% had 5-20 MC, 43% had a history of atopic dermatitis (AD), 5% were using topical steroids, 25.5% had coexistent AD, 13% had giant MC (>5 mm), 21% had inflammatory MC, and 19% had MC surrounded by eczema. Bathing with siblings was associated with a higher number of MC. A history of AD was associated with the presence of MC surrounded by eczema. The use of topical steroids was associated with a higher risk of relapse. There was no relation between environmental factors (MC in surrounding people, going to the swimming pool, sports practice) and the number of lesions or between environmental factors and the number of recurrences. CONCLUSION: Atypical lesions are frequent. Bathing with siblings is associated with a higher number of MC. Topical steroid use increases the risk of relapses. AD prevalence is higher than in the general population.

Effects of azacitidine in 93 patients with IDH1/2 mutated acute myeloid leukemia/myelodysplastic syndromes: a French retrospective multicenter study.

Isocitrate dehydrogenase 1 (IDH1) and 2 (IDH2) mutations in Myeloid Neoplams (MNs) exhibit DNA hypermethylation via 2-hydroxyglutarate (2HG) over-production. Clinical impact of azacitidine (AZA) remains inconsistent in IDH1/2-mutated MNs and the potential of serum 2HG as a suitable marker of response to AZA is unknown. To address these questions, we retrospectively analyzed 93 MNs patients (78 AML, 11 MDS, 4 CMML) with IDH1/2 mutations treated with AZA. After a median of 5 cycles of AZA, overall response rate was 28% (including 15% complete remission) and median OS was 12.3 months (significantly shorter in AML compared to MDS/CMML patients). In multivariate analysis of AML patients, DNMT3A mutation was associated with shorter OS while IDH1/2 mutation subtypes had no independent impact. No difference was observed in serum 2HG levels upon AZA treatment between responding and refractory patients suggesting that serum 2HG cannot be used as a surrogate marker of AZA response.

Use of 5-azacitidine for therapy-related myeloid neoplasms in patients with concomitant active neoplastic disease.

BACKGROUND: Patients diagnosed with therapy-related myeloid neoplasms (TRMN) with concomitant active neoplastic disorder (CAND) are usually proposed for best supportive care (BSC). We evaluated the feasibility of using 5-azacytidine (AZA) in this setting. METHODS: All patients referred to Gustave Roussy between 2010 and 2015 for TRMN diagnosis (less than 30% blast) and eligible for AZA treatment were included. Patients with CAND proposed for BSC were also described. Patient's outcomes were analyzed based on the presence or not of a CAND. RESULTS: Fifty-two patients with TRMN were analyzed, including 19 patients with CAND (14 eligible for AZA) and 33 without CAND eligible for AZA. The 5 patients with CAND ineligible for AZA had a worst performance status (p=0.016) at diagnosis and a shorter overall survival (OS) (0.62 months). Baseline characteristics of patients eligible for AZA were similar in the 2 groups except a trend for best performance status in patients with CAND (p=0.06). Overall response rate (71.4% vs 60.3%), transfusion independence (50.0% vs 45.5%) and OS (12.7 months vs 10.8 months) were similar between patients with and without CAND respectively (p=ns). CONCLUSION: Here we report the feasibility and efficacy of AZA for selected patients with TRMN and a CAND.

Pregnancy loss: French clinical practice guidelines.

In intrauterine pregnancies of uncertain viability with a gestational sac without a yolk sac (with a mean of three orthogonal transvaginal ultrasound measurements <25mm), the suspected pregnancy loss should only be confirmed after a follow-up scan at least 14 days later shows no embryo with cardiac activity (Grade C). In intrauterine pregnancies of uncertain viability with an embryo <7mm on transvaginal ultrasound, the suspected pregnancy loss should only be confirmed after a follow-up scan at least 7 days later (Grade C). In pregnancies of unknown location after transvaginal ultrasound (i.e. not visible in the uterus), a threshold of at least 3510IU/l for the serum human chorionic gonadotrophin assay is recommended; above that level, a viable intrauterine pregnancy can be ruled out (Grade C). Postponing conception after an early miscarriage in women who want a new pregnancy is not recommended (Grade A). A work-up for women with recurrent pregnancy loss should include the following: diabetes (Grade A), antiphospholipid syndrome (Grade A), hypothyroidism with anti-thyroid peroxidase (anti-TPO) and anti-thyroglobulin (anti-Tg) antibodies (Grade A), vitamin deficiencies (B9, B12) (Grade C), hyperhomocysteinaemia (Grade C), hyperprolactinaemia (Grade B), diminished ovarian reserve (Grade C), and a uterine malformation or an acquired uterine abnormality amenable to surgical treatment (Grade C). The treatment options recommended for women with a missed early miscarriage are vacuum aspiration (Grade A) or misoprostol (Grade B); and the treatment options recommended for women with an incomplete early miscarriage are vacuum aspiration (Grade A) or expectant management (Grade A). In the absence of both chorioamnionitis and rupture of the membranes, women with a threatened late miscarriage and an open cervix, with or without protrusion of the amniotic sac into the vagina, should receive McDonald cerclage, tocolysis with indomethacin, and antibiotics (Grade C). Among women with a threatened late miscarriage and an isolated undilated shortened cervix (<25mm on ultrasound), cerclage is only indicated for those with a history of either late miscarriage or preterm delivery (Grade A). Among women with a threatened late miscarriage, an isolated undilated shortened cervix (<25mm on ultrasound) and no uterine contractions, daily treatment with vaginal progesterone up to 34 weeks of gestation is recommended (Grade A). Hysteroscopic section of the septum is recommended for women with a uterine septum and a history of late miscarriage (Grade C). Correction of acquired abnormalities of the uterine cavity (e.g. polyps, myomas, synechiae) is recommended after three early or late miscarriages (Grade C). Prophylactic cerclage is recommended for women with a history of three late miscarriages or preterm deliveries (Grade B). Low-dose aspirin and low-molecular-weight heparin at a preventive dose are recommended for women with obstetric antiphospholipid syndrome (Grade A). Glycaemic levels should be controlled before conception in women with diabetes (Grade A).

[Shoulder dystocia: Guidelines for clinical practice--Short text]. / Dystocie des épaules : recommandations pour la pratique clinique--Texte court.

OBJECTIVES: To determine the available evidence to prevent and treat shoulder dystocia to attempt to decrease its related neonatal and maternal morbidity. MATERIALS AND METHODS: The PubMed database, the Cochrane Library and the recommendations from the French and foreign obstetrical societies or colleges have been consulted. RESULTS: Shoulder dystocia, defined as a vaginal delivery that requires additional obstetric maneuvers to deliver the fetus after the head has delivered and gentle traction has failed, complicates 0.5-1 % of vaginal deliveries. Risks of brachial plexus birth injury (LE3), clavicle and humeral fracture (LE3), perinatal asphyxia (LE2), hypoxic-ischemic encephalopathy (LE3) and perinatal mortality (LE2) are increased after shoulder dystocia. Its main risk factors are previous shoulder dystocia and macrosomia, but they are poorly predictive; 50 % to 70 % of shoulder dystocia cases occur in their absence, and the great majority of deliveries when they are present are not associated with shoulder dystocia. No study has proven that the correction of these risk factors (except gestational diabetes) would reduce the risk of shoulder dystocia (SD). Physical activity is recommended before and during pregnancy to reduce the occurrence of some risk factors for shoulder dystocia (grade C). In obese patients, physical activity should be coupled with dietary measures to reduce fetal macrosomia and weight gain during pregnancy (grade A). In case of gestational diabetes, diabetes care is recommended (diabetic diet, glucose monitoring, insulin if needed) (grade A) as it reduces the risk of macrosomia and shoulder dystocia (LE1). In order to avoid shoulder dystocia and its complications, only two measures are proposed. Induction of labor is recommended in case of impending macrosomia if the cervix is favourable and gestational age greater than 39 weeks of gestation (professional consensus). Cesarean delivery is recommended before labor in case of EFW greater than 4500g if associated with maternal diabetes (grade C), EFW greater than 5000g in the absence of maternal diabetes (grade C), history of shoulder dystocia associated with severe neonatal or maternal complications (Professional consensus), and finally during labor, in case of fetal macrosomia and failure to progress in the second stage, when the fetal head is above a +2 station (grade C). In case of shoulder dystocia, it is recommended not to pull excessively on the fetal head (grade C), do not perform uterine expression (grade C) and do not realize inverse rotation of the fetal head (professional consensus). McRoberts' maneuver, with or without a suprapubic pressure, is recommended in the first line (grade C). In case of failure, if the posterior shoulder is engaged, Wood's maneuver should be performed preferentially; if the posterior shoulder is not engaged, delivery of the posterior arm should be performed preferentially (professional consensus). It seems necessary to know at least two maneuvers to perform in case of shoulder dystocia unresolved by the maneuver of McRoberts (professional consensus). Pediatrician should be immediately informed in case of shoulder dystocia. The initial clinical examination should search complications such as brachial plexus birth injury or clavicle fracture (professional consensus). In absence of neonatal complication, monitoring of the neonate is not modified (professional consensus). The implementation of a practical training using simulation and concerning all caregivers of the delivery room is associated with a significant reduction in neonatal (LE3) but not maternal (LE3) injury. CONCLUSION: Shoulder dystocia remains a non-predictable obstetrics emergency. All physicians and midwives should know and perform obstetric maneuvers if needed quickly but without precipitation. A training program using simulation for the management of shoulder dystocia is encouraged for the initial and continuing formation of different actors in the delivery room (professional consensus).

Wegener's granulomatosis. Dermatological manifestations in 75 cases with clinicopathologic correlation.

BACKGROUND AND DESIGN: Mucosal and cutaneous manifestations of Wegener's granulomatosis (WG) are usually described separately. Both frequently occur at any time of the illness. The aim of this work was to analyze, retrospectively, dermatologic symptoms of 75 WG cases encountered from 1973 through 1992. All patients fulfilled the American College of Rheumatology criteria for WG. We compared clinical and histologic findings and looked for a relationship between these manifestations, disease activity, and other symptoms of WG. RESULTS: Thirty-five patients had skin or mucosa involvement. Clinical features were palpable purpura (26 cases), oral ulcers (15), skin nodules (six), skin ulcers (five), necrotic papules (five), gingival hyperplasia (three), pustules (two), palpebral xanthoma (two), genital ulcer (one), digital necrosis (one), and livedo reticularis (one). Pathologic findings depended on clinical aspects. Thirty-five involved skin or mucosa biopsy specimens were obtained from 24 patients. Nongranulomatous vasculitis was associated with purpuric lesions. Granulomatous inflammation was associated with nonpurpuric lesions. Dermatologic manifestations were associated with a higher frequency of articular and renal involvement (68% vs 25%; 80% vs 47%, respectively). Except for xanthoma, onset of skin or mucosa lesions indicated active systemic disease. These manifestations responded well to steroids and cyclophosphamide. CONCLUSIONS: Various dermatologic manifestations are frequently observed in WG. They have distinctive pathologic features and usually indicate the presence of active systemic disease, especially with kidney and joint involvement.

Microassay of propranolol enantiomers and conjugates in human plasma and urine by high-performance liquid chromatography after chiral derivatization for pharmacokinetic study.

A microdetermination of propranolol enantiomers and of their glucuronide and sulphate conjugates in human plasma and urine by reversed-phase HPLC after chiral derivatization is described. After extraction from 100 microliters of plasma or urine with racemic 4-methylpropranolol as internal standard (I.S.), the enantiomers are derivatized with R(+)-phenylethylisocyanate as chiral derivatization reagent. Chromatography is performed on Novapak C18 column with fluorescence detection. Glucuronide and sulphate conjugates are cleaved prior to extraction by incubating, respectively, the samples with glucuronidase-arylsulphatase and saccharic acid 1-4 lactone as specific glucuronidase inhibitor. The retention times of propranolol and I.S. enantiomer derivatives are short (tR = 5.5-6.2 min and 8.8-10.1 min, respectively). The diastereomeric derivatives are very stable and show good peak symmetry and resolutions (RS = 2 and 2.2). The use of 4-methylpropranolol as I.S. improves significantly relative standard deviations (RSD: 1.7-5.1). Sensitivity is about 1 ng ml-1 per enantiomer. The method is applied to pharmacokinetic studies of racemic propranolol in human plasma and urine. S-propranolol and its conjugates show higher concentrations than R-propranolol and its conjugates in plasma and urine.

[Cutaneous necrosis caused by hydrofluoric acid]. / Nécroses cutanées à l'acide hydrofluorique.

INTRODUCTION: Hydrofluoric acid is a fluoride-substituted compound used in the chemical industry. Burns and hypocalcaemia result from ingestion or contact with the skin or mucosal membranes. We observed burns and skin necrosis on the hands after home use of low-concentration hydrofluoric acid. CASE REPORT: A 57-year-old woman consulted in February 1994 for oedema, erythema and very painful burns of the palms of both hands. The day before, she had used a home-made furniture cleanser containing 5 p. 100 hydrofluoric acid. At admission, calcium and radiography of the two hands were normal. She was given a topical application of 5 p. 100 calcium chloride. The clinical course was favourable with squamation of both palms then necrotic lesions of the pulp on the 1st, 2nd and 3rd fingers. DISCUSSION: Such exposure in a household situation is unusual. Hydrofluoric acid has two dangerous mechanisms of action. First it is a caustic substance producing late-onset burns and secondly hypocalcaemia results from precipitation of insoluble calcium fluoride. The risk of hypocalcaemia is greatest when a large area of the skin is exposed. Prognosis depends on early treatment based on prevention of hypocalcaemia by abundant washing of the teguments and permanent application of a 5 p. 100 calcium gluconate solution associated with local skin treatments. Careful follow-up is required with regular calcium chemistries.

[Neutrophilic eccrine hidradenitis associated with relapse of acute myeloblastic leukemia]. / Hidradénite eccrine neutrophilique associée à une rechute de leucémie aiguë myéloblastique.

BACKGROUND: Neutrophilic eccrine hidradentitis is a recently described clinical entity. Most reported cases have occurred in patients given chemotherapy for acute myelogenous leukemia, suggesting a drug induced mechanism. Some authors have considered however that neutrophilic eccrine hidradenitis belongs to the group of neutrophilic dermatoses. CASE REPORT: We observed neutrophilic eccrine hidradentitis in a 48-year-old man which developed when he suffered a relapse of acute leukemia. He had not been given chemotherapy in the preceding months. DISCUSSION: This case favors the hypothesis that neutrophilic eccrine hidradenitis is associated with myeloid hemotology disorders and not a complications secondary to treatment.

[Lichen planus in children: 12 cases]. / Lichen plan de l'enfant. 12 cas.

OBJECTIVE: Lichen planus is in children uncommon and poorly understood. The classical description is comparable to lichen planus in adults. We conducted a retrospective analysis of 12 cases in children. PATIENTS AND METHODS: Twelve children with lichen planus consulted the Saint-Louis or Robert-Debré hospitals between February 1994 and March 1996. Data collected included: age, sex, ethnic origin, drug use, anti-hepatitis vaccination status, disease history, physical examination, skin histology, liver tests, hepatitis B and C serology, treatment and outcome. Histological proof was obtained in all cases but one (a child with isolated ungueal involvement whose sister had histologically proven ungueal lichen planus). RESULTS AND DISCUSSION: The clinical features classically described in adults were atypical in all our childhood cases. A rapidly extensive eruption was the main sign in 6 cases. The localizations were unusual with lesions involving all four limbs and the trunk as well as the face in 5 cases and the scalp in 1. Mucosal involvement, observed in 65 p. 100 of adult cases was only found in one of our children. Unguel involvement also appears to be uncommon in children. The etiological pattern was also unusual since we did not observe a single case related to drugs or hepatitis B or C infection. Three children developed a lichen eruption after anti-hepatitis B infection. Four other cases of lichen planus after anti-hepatitis B vaccination have been reported in the literature. Mean delay between the booster vaccination and onset of eruption is reported to be 40 days. The increased incidence of childhood lichen planus in tropical zones suggests ethnic, genetic and climatic factors may be involved. Prognosis is poorly defined in the literature. Certain authors emphasize the long duration of the disease and resistance to treatment in cases of childhood lichen planus. Currently, there is no consensus on treatment. Dermocorticoids in combination with antihistaminics are usually prescribed. General corticosteroid therapy would appear to be warranted in extensive progressive forms with important functional and esthetic impact (scalp involvement with cicatricial alopecia, pigmentation sequellae). The role of other drugs, particularly retinoids, remains to be defined. This retrospective series was not statistically significant. Data in the literature are rather discordant, emphasizing the need for a prospective analysis to acquire a better understanding of the real incidence of childhood lichen planus and better define the therapeutic strategy.

[Early recurrent miscarriage: Evaluation and management]. / Fausses couches précoces « à répétition ¼ : bilan et prise en charge.

OBJECTIVE: To establish recommendations for early recurrent miscarriages (≥3 miscarriages before 14weeks of amenorrhea). MATERIALS AND METHODS: Literature review, establishing levels of evidence and recommendations for grades of clinical practice. RESULTS: Women evaluation includes the search for a diabetes (grade A), an antiphospholipid syndrome (APS) (grade A), a thyroid dysfunction (grade A), a hyperprolactinemia (grade B), a vitamin deficiency and a hyperhomocysteinemia (grade C), a uterine abnormality (grade C), an altered ovarian reserve (grade C), and a couple chromosome analysis (grade A). For unexplained early recurrent miscarriages, treatment includes folic acid and progesterone supplementation, and a reinsurance policy in the first quarter (grade C). It is recommended to prescribe the combination of aspirin and low-molecular-weight heparin when APS (grade A), glycemic control in diabetes (grade A), L-Thyroxine in case of hypothyroidism (grade A) or the presence of thyroid antibodies (grade B), bromocriptine if hyperprolactinemia (grade B), a substitution for vitamin deficiency or hyperhomocysteinemia (grade C), sectionning a uterine septum (grade C) and treating an uterine acquired abnormality (grade C). CONCLUSION: These recommendations should improve the management of couples faced with early recurrent miscarriages.