Omalizumab in patients with chronic spontaneous urticaria nonresponsive to H1-antihistamine treatment: results of the phase IV open-label SUNRISE study.

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

Les traitements systémiques de la dermatite atopique: Systemic treatments of atopic dermatitis.

The treatment of atopic dermatitis is based on the use of topical steroids and emollients. When AD is resistant to a well-conducted topical treatment, phototherapy or systemic therapeutics can be used: ciclosporin, methotrexate, azathioprine or mycophenolate mofetil. However, the therapeutic landscape of AD is changing dramatically because of the approval of dupilumab (an anti-IL4/IL13 biologic therapy) and the possible future arrival of other biologicals (anti-IL13, anti-IL31…), and JAK inhibitors. © 2019 Elsevier Masson SAS. All rights reserved.

Factors associated with the choice of the first biologic in psoriasis: real-life analysis from the Psobioteq cohort.

BACKGROUND: Decision-making is a complex process. The aim of our study was to assess factors associated with the choice of the first biological treatment in patients with moderate-to-severe psoriasis. METHODS: Data on all patients included in the French prospective, observational, cohort, Psobioteq and initiating a first biologic prescription between July 2012 and July 2016 were analysed. Demographic information and clinical features were collected during routine clinical assessments by the dermatology team at the recruiting centres using a standardized case report form. The primary outcome was the nature of the first biologic treatment. Four groups were identified as follows: adalimumab, etanercept, ustekinumab and infliximab groups. Factors associated with the choice of the first biological agent were determined by a multinomial logistic regression model adjusted on year of inclusion. RESULTS: The study population included the 830 biological-naïve patients who initiated a first biological agent. The mean age was 46.6 years (±SD 13.9), and 318 patients (38.3%) were female. The most commonly prescribed biologic was adalimumab: 355 (42.8%) patients, then etanercept (n = 247, 29.8%), ustekinumab (n = 194, 23.4%) and infliximab (n = 34, 4.0%). In the multinomial logistic regression analysis, patients were significantly more likely to receive adalimumab if they had a severe psoriasis as defined by baseline PASI or if they had psoriatic arthritis compared to etanercept (aOR, 0.42; 95% CI, 0.16-1.07) and ustekinumab (aOR, 0.15; 95% CI, 0.04-0.52). Patients were significantly more likely to receive ustekinumab (aOR, 2.39; 95% CI, 1.04-5.50) if they had a positive screening for latent tuberculosis compared to adalimumab. Younger patients were also more likely to receive ustekinumab. Patients with chronic obstructive pulmonary disease were more likely to be prescribed ustekinumab or etanercept compared to adalimumab. There was a trend in favour of etanercept prescription in patients with cardiovascular comorbidities, metabolic syndrome and in patients with a history of cancer. CONCLUSION: We identified patient- and disease-related factors that have important influence on the choice of the first biological agent in clinical practice. Clinicians appear to have a holistic approach to patient characteristics when choosing a biological agent in psoriasis.

[Current and upcoming treatments of adult atopic dermatitis]. / L'actuel et le futur du traitement de la dermatite atopique de l'adulte.

The treatment of atopic dermatitis in adults is based on the use of topical steroids and emollients. When AD is resistant to a well-conducted topical treatment, phototherapy or systemic treatments can be used: ciclosporin, methotrexate, azathioprine or mycophenolate mofetil. The therapeutic landscape of adult AD is about to change and even be revolutionized by the imminent arrival of new treatments: topical phosphodiesterase 4 inhibitors, topical or systemic JAK inhibitors, anti-IL-4 and/or antiIL-13 biotherapies (dupilumab, tralokinumab, lebrikizumab), anti-IL-31 (nemolizumab), anti-TSLP.

[Sneddon-Wilkinson disease: efficacy of intermittent adalimumab therapy after lost response to infliximab and etanercept]. / Maladie de Sneddon-Wilkinson échappant à l'infliximab et à l'étanercept: efficacité de l'adalimumab.

BACKGROUND: Sneddon-Wilkinson disease (SWD) is a rare chronic neutrophilic dermatosis. The first-line treatment is dapsone but resistance to treatment may sometimes pose a challenge. CASE REPORT: We report a multidrug-resistant patient who responded dramatically before gradually losing response to infliximab and then etanercept. Complete remission was again obtained with adalimumab. DISCUSSION: Our case confirms the previously reported dramatic efficacy of anti-TNF biological agents in recalcitrant SWD but highlights the possibility of subsequent loss of response. Furthermore, it illustrates the efficacy of adalimumab in this indication.

Laboratory effect on platelet activity within 24 h of the first 300-mg oral dose of aspirin given in hospital during the acute phase of ischemic cerebral events.

BACKGROUND AND PURPOSE: Aspirin is the most commonly used antiplatelet treatment during the acute phase of cerebral ischemic events. It inhibits the production of thromboxane (TX) A(2), a powerful platelet activator. Despite this protection, early ischemic recurrences are frequent and considered clinical failures of this therapy. Only a few trials have focused on the use of antiplatelet therapy during this phase, and none has described the laboratory effect of the first dose of aspirin given after an ischemic cerebral event. However, this study may help clinicians to understand the mechanisms of early recurrences, and to design new therapeutic strategies, in particular for patients already treated with a daily dose of aspirin. METHOD: We studied laboratory parameters of the first 300-mg oral dose of aspirin given within 48 h after an ischemic cerebral event. Two blood samples were taken from all of the patients: the first during the third hour following aspirin intake (T1) and the second during the twenty-fourth hour (T2). For patients already treated with a daily dose of aspirin, a supplementary sample was taken before aspirin intake (T0). Platelet reactivity was studied on the basis of serum TXB(2) levels, a metabolite of TXA(2), and light transmission aggregometry after stimulation of platelet-rich plasma by arachidonic acid and by two concentrations of collagen, i.e. 2 µg/ml (Col2), dependent on the TXA(2) pathway, and 20 µg/ml (Col20), independent of the TXA(2) pathway. Results with Col2 were related to results with Col20 (Col2/20 ratio) to limit the impact of variations induced by the effects of preanalytical conditions. RESULTS: Fifty patients were included. TXB(2) values (p < 0.001) and relative values of the Col2/20 ratio (p = 0.037) were significantly higher at T2 compared to T1. For patients already treated with aspirin, TXB(2) levels (p < 0.001) were significantly lower at T1 compared to T0, and the Col2/20 ratio tended to decrease (p = 0.096). CONCLUSION: Platelet reactivity recovers within 24 h following the first 300-mg oral dose of aspirin during the acute phase of a cerebral ischemic event as demonstrated by an increase in TXB(2) levels, and the Col2/20 ratio, at T2 compared to T1. This would favor early ischemic recurrences. However, for patients already treated with aspirin, this dose is able to decrease TXB(2) levels and to complete the inhibition of the TXA(2) pathway, which shows the utility of this prescription in this case.

308-nm excimer lamp vs. 308-nm excimer laser for treating vitiligo: a randomized study.

BACKGROUND: The 308-nm excimer laser and 308-nm excimer lamp have both been shown to be effective in treating vitiligo but a direct comparison has never been performed. OBJECTIVES: To test the equivalence of these two devices for treating nonsegmental vitiligo. PATIENTS AND METHODS: A randomized monocentric study was undertaken. One lesion was treated with the 308-nm excimer laser and its counterpart with the 308-nm excimer lamp. Lesions were treated twice weekly with the same dose on both sides for a total of 24 sessions. The evaluation was done by two independent physicians blinded to the treatment on direct light and ultraviolet light photos. RESULTS: Twenty patients were included: 17 completed the study and 104 lesions were treated. The two treatments showed similar results in terms of efficacy for a repigmentation of at least 50% (P = 0.006). The lamp induced more erythema than the laser. CONCLUSIONS: The 308-nm excimer lamp and laser showed a similar efficacy in treating vitiligo. For the same fluence, the lamp induced more erythema suggesting photobiological differences between the two devices.

The effects of exercise and protein-energy supplements on body composition and muscle function in frail elderly individuals: a long-term controlled randomised study.

Fighting against inactivity and inadequate nutritional intake are of utmost importance in the elderly. To our knowledge, the few studies which have been performed were conducted for only a short period and the results do not permit formal conclusions to be drawn. We therefore tried to fill this gap in our knowledge by determining whether an intervention combining an acceptable progressive exercise programme and nutritional supplements would be feasible for a long-term period in the very frail elderly, and would bring about concomitant benefits in body composition and muscle power. Accordingly, this exercise and nutritional combination was assessed in the frail elderly in a 9-month randomised trial with a factorial design. Fifty-seven elderly volunteers over 72 years, from sixteen retirement homes in Lyon, France participated in the study. Dietary supplements were compared with placebo, and physical exercise was compared with memory training. Main outcome measures were fat-free mass (FFM) and muscle power. FFM was determined by labelled water, and muscle power was measured by a leg-extensor machine. At 9 months, the compliance was 63 % for exercise sessions, and 54 % for nutritional supplements. In patients with dietary supplements, muscle power increased by 57 % at 3 months (P=0.03), and showed only a tendency at 9 months; although FFM increased by 2.7 % at 9 months, the difference was not significant (P=0.10). Exercise did not improve muscle power at 9 months, but improved functional tests (five-time-chair rise, P=0.01). BMI increased with supplements (+3.65 %), but decreased with placebo (-0.5 %) at 9 months (P=0.007). A long-term combined intervention is feasible in frail elderly individuals with a good rate of compliance. Nutritional supplements and exercise may improve muscle function. Despite no significant results on FFM, due to the limited number of volunteers, combined intervention should be suggested to counteract muscle weakness in the frail elderly.

Pulmonary function in men after repeated sessions of oxygen breathing at 0.25 MPa for 90 min.

HYPOTHESIS: We wanted to evaluate the pulmonary effects of discontinuous oxygen breathing (15 min O2, 2 min air breaks, 15:2), at 0.25 MPa once a day for 90 min O2 (6 sequences) over 10 d. This sequence, which has never been evaluated, is currently used in our hyperbaric therapy center. METHODS: Clinical and functional pulmonary status (questionnaire, spirometry, flow/volume loop, pulmonary diffusing capacity for carbon monoxide) was assessed in 10 non-smoking healthy volunteers after one exposure at 0.25 MPa consisting of 90 min of discontinuous oxygen breathing (15:2) and in 10 non-smoking patients who received a hyperbaric treatment consisting of 90 min of the same discontinuous O2 breathing (15:2) once a day over 10 d. The patients received daily intravenous methylprednisolone (1 mg x kg(-1)) and nicergoline (60 mg). RESULTS: There were no respiratory symptoms in either group. As expected, for a single exposure of that duration, lung function did not change in volunteers; however, a significant decrease in maximal expiratory flows (MEF) at 50 (-15%) and 25% (-33%) of forced vital capacity (p < 0.05) without change in forced vital capacity (FVC) appeared in patients treated over 10 d. CONCLUSION: Repetition of the 15:2 oxygen breathing sequence for 90 min once a day over 10 d led to greater flow limitation in peripheral airways than reported after continuous oxygen breathing of 210 min at 0.3 MPa which showed a 7% decrement in MEF50 and a 12% decrement in MEF25. No studies reporting these indexes were found in the 0.2-0.25 MPa range. Similar decrements in MEF50 and MEF25 with steady FVC have been reported after 14 d of daily hyperbaric therapy (0.24 MPa) with 30:5 sequence (-9% and -13%, respectively), 80% of the patients were symptom free. Similarily, our patients were all symptom free and remained so 1 yr after the study, hence, this toxicity is of weak clinical significance in subjects free of inflammatory lung diseases. HBO therapy, though safe, is not totally without effect on the lung.

Polyadenylic-polyuridylic acid plus locoregional radiotherapy versus chemotherapy with CMF in operable breast cancer: a 14 year follow-up analysis of a randomized trial of the Fédération Nationale des Centres de Lutte contre le Cancer (FNCLCC).

With a median follow-up of 14 years, the combination of polyadenylic-polyuridylic acid plus locoregional radiotherapy (257 patients) has significantly improved disease-free survival (p = 0.03) and significantly reduced the incidence of metastases (p = 0.04) when compared to CMF alone (260 patients), in women with operable breast cancer. The trial does not, however, permit an appreciation of the respective role of radiotherapy and PolyAU in these results.

[Psoriasis. Treatment]. / Psoriasis. Traitement.

FUNDAMENTALS: The aim of treatment in psoriasis is to reduce the degree of extension to a point compatible with the patients social, occupational and personal lifestyle. The patient should be informed that there is no curative treatment. A good patient-doctor relationship is required for the patient to understand that the proposed treatment can provide symptomatic relief but must take into account an optimal balance between treatment benefit and risk. Therapeutic abstention must be recognized as a possibility. In all cases, efforts must be made to recognize and eliminate if possible any favoring factors. A TWO-PHASE TREATMENT: Initially, the aim of the treatment is to induce an involution of the active lesions. A second phase is aimed at avoiding subsequent fiare-ups. Local treatments: Local care should always be preferred in patients with limited lesions. Keratolytic agents, dermocorticoids and vitamin D3 derivatives can be used. Topical retinoids, particularly tazarotene are in the development stage. SYSTEMIC TREATMENTS: Systemic treatments should be reserved for extensive psoriasis and for failure after well-conducted local care. Photoherapy, particularly PUVA-therapy and more recently narrow-spectrum UVB-therapy play an important role. Systemic retinoids can be used alone or in combination with PUVA-therapy. The risks of methrotrexate and cyclosporin impose their use exclusively in specialized centers. Several other treatments are still in the experimental stage, particularly promising highly selective immunotherapy.

Anaemia and iron deficiency in athletes. Practical recommendations for treatment.

Trained athletes frequently experience low levels of blood haemoglobin (13 to 14 g/100ml in men and 12 g/100ml in women) plus low haematocrit and low ferritin levels. These parameters define the concept of 'sports anaemia'. Low iron levels may be due to mechanical haemolysis, intestinal bleeding, haematuria, sweating, low iron intake or poor intestinal absorption. The resulting decrease in blood gas transport and muscle enzyme activity impairs performance. The concept of sports anaemia can be criticised. Simply measuring the blood levels does not take into account the haemodilution that occurs in athletes because of training. The lack of these measurements makes it difficult to diagnose anaemia or evaluate any treatment. Anaemia is treated by preventing decreased iron stores through a balanced food intake or iron supplements. Self-medications must be discouraged because of intolerance, risk of overdose and many other drug interactions.

Effects of indomethacin and polyunsaturated fatty acid diet on exercise-induced hypoxaemia in master athletes.

We have previously reported a reduction in exercise-induced hypoxaemia following polyunsaturated fatty acid supplementation (PUFA). Although this might have been explained by increases in membrane fluidity, a clear explanation could not be provided due to potentially confounding influences of series-2 prosta- glandin mediated effects resulting from PUFA. In this investigation, ten master athletes [mean age 48.1 (SEM 6) years, maximal oxygen uptake (VO2max) 3.39 (SEM 0.21) l x min(-1)] completed a maximal cycling test (Ctrl) which was repeated after the administration of 150 mg of indomethacin to inhibit prostaglandin synthesis, both before and after 6 weeks of 3.66-g PUFA x day(-1). Cardiorespiratory parameters were obtained simultaneously with brachial arterial blood sampling for partial pressure of oxygen in arterial blood (PaO2), partial pressure of carbon dioxide in arterial blood (PaCO2), pH, oxygen saturation in arterial blood and lactate concentration determinations. A significant decrease in PaO2 (mmHg) from rest [93 (SEM 1.5)] was observed for exercise intensities of more than 40% VO2max in Ctrl reaching 75.9 (SEM 2.1) at VO2max. PUFA resulted in a 5.0 (SEM 0.68) mmHg upward shift (P < 0.05) in the PaO2-oxygen uptake relationship, reducing the difference in partial pressure of oxygen between alveolar air and arterial blood (P(A-a)O2) at VO2max [Ctrl 36 (SEM 1.6) vs PUFA 33 (SEM 2.2) mmHg] while PaCO2, remained unchanged. Indomethacin had no effect on either PaO2, ideal partial pressure of oxygen in alveolar gas or P(A-a)O2 in either Ctrl or after PUFA. In contrast, the fall in pH was significantly reduced after indomethacin while VCO2, PaCO2 and lactacidaemia remained unchanged. These observations confirm an effect of PUFA on exercise PaO2 behaviour which does not appear to be mediated by the influence of a series-2 prostaglandin.

Exercise-induced hypoxaemia in master athletes: effects of a polyunsaturated fatty acid diet.

Exercise-induced hypoxaemia (EIH) has been associated with an oxygen diffusion limitation. Because polyunsaturated fatty acids (PUFA) administration can modify cell membrane fluidity, we hypothesized that the importance of EIH could be reduced after a 6-week PUFA diet. Resting pulmonary functions and a maximal cycling test were performed before and after the diet, in eight master athletes -48 (SD 6 years)-. The partial pressure of O2 in arterial blood (PaO2), alveolar ventilation (VA) and ideal alveolar-arterial oxygen partial pressure difference (P(Ai-a) O2) were obtained at each exercise intensity. The extent of EIH at maximal exercise was significantly lower after PUFA [PaO2-17.2 (SEM 1.9) vs -12.9 (SEM 2.2)]. Before PUFA, VA accounted for 50% of the variance in the fall in P (Ai-a) for intensities below 80% maximal oxygen uptake (VO2max) and P(Ai-a)O2 for 60% between 70% and 100% VO2max. After PUFA, the reduction in EIH was highly correlated (r2 = 0.85; P < 0.001) to resulting changes in P(Ai-a)O2 and resting pulmonary diffusing capacity (DLCO)/VA but not with changes in ideal alveolar partial pressure of oxygen. The improvement in EIH following PUFA could be related to an increase in alveolar-arterial oxygen conductance following improved pulmonary diffusion.

A radiolabelled iodobenzamide for malignant melanoma staging.

123I-N-(di-ethylamino-2-ethyl) 4 iodobenzamide (I-BZA) has been put forward by the Clermont-Ferrand INSERM U71 group (France) as a tracer for malignant melanoma. We report on the clinical results obtained in 56 studies performed on 48 patients. Whole body scans along with spot views were obtained after injection of 185 MBq of I-BZA. The scans were read by three independent observers and correlated to the clinical findings and the other imaging modalities available, taking into account all lesions larger than 1 cm. Patients were classified into two groups on the basis of a post-treatment survey of patients: group I, in complete remission (24 scans); group II: documented metastases (32 scans). In group 1, 21 studies were truly negative. However, three studies showed positive results. Only one turned out to be a false positive (specificity 95%), the other two revealed unknown lesions and modified the patients' management. In group II, 73% of the known metastases were detected with higher sensitivities (> 80%) for eye and orbit, lung and abdomen. One false positive was reported and four new lesions were detected. I-BZA scintigraphy has the same sensitivity as immunoscintigraphy with higher specificity and without the risk of xenoimmunization. It is a useful tool for staging malignant melanoma which can improve patient management.

["Bronze baby" syndrome]. / Le syndrome du "bébé de couleur bronze".

"Bronze baby" syndrome is a rare complication of phototherapy for neonatal jaundice occurring due to modified liver function, particularly cholestasis, of various origins. We report a case which occurred in a premature infant who developed a grey-brown coloration during phototherapy. The infant had haemolytic jaundice due to Rhesus incompatibility complicated by cholestasis of thick bile fluid. Abnormal accumulation of unexcreted photoproducts due to the cholestasis appeared to be the cause of the bronze coloration. The clinical course was favourable and the skin coloration returned to normal a few weeks after the end of the phototherapy. It is essential to identify the underlying liver disease in order to determine the prognosis of this syndrome.

Polyadenylic-polyuridylic acid plus locoregional and pelvic radiotherapy versus chemotherapy with CMF as adjuvants in operable breast cancer. A 6 1/2 year follow-up analysis of a randomized trial of the French Federation of Cancer Centers (F.F.C.C.).

In this study, patients with operable breast cancer T2 or T3, treated by mastectomy + axillary dissection and with invaded axillary nodes (N+), were randomized to receive either: 1) postoperative locoregional and pelvic radiotherapy (RX) and Poly(A).Poly(U) (AU), 60 mg IV once a week for 6 weeks, or 2) CMF (cyclophosphamide 100 mg/sqm P.O. on days 1-14, methotrexate 40 mg/sqm IV on day 1 and 8, fluorouracil 600 mg/sqm IV on day 1 and 8; monthly cycle, for 6 months. Between March 1982 and December 1985, 517 patients were enrolled, 257 of whom were treated by RX + AU and 260 with CMF. The main clinical, pathological and prognostic characteristics were equally distributed in the two groups. The present analysis was conducted after a mean follow-up of 69 months (S.D. = 13). There was no significant difference in overall survival (OS) between the two groups (test adjusted by center and menopausal status); the five-year OS rate was 74% in the RXAU group and 77% in the CMF group. Relapse-free survival (RFS) was significantly higher (p = 0.05) in the RXAU group compared to the MCF group; the five-year RFS rates were 57% and 46% in the two groups respectively. This short, well-tolerated combined RXAU treatment appears to be as efficient as CMF and might offer an alternative to chemo- or hormonotherapy, in case of contraindications to these treatments.