Fetal death in utero and miscarriage in a patient with Crohn's disease under therapy with ustekinumab: case-report and review of the literature.

BACKGROUND: Ustekinumab is a fully human monoclonal antibody against the p40 subunit of interleukin (IL) 12 and 23 which is involved in the pathogenesis of several inflammatory diseases. Ustekinumab is approved for psoriasis and psoriatic arthritis treatment and has been successfully evaluated in phase II and III trials for patients with Crohn's disease (CD). CASE PRESENTATION: We report here the case of a patient who became pregnant during treatment with ustekinumab for a refractory CD and which ended in miscarriage. CONCLUSION: Ustekinumab is a relatively new pharmacotherapy and in addition to this clinical case, we reviewed the published literature concerning the use of this treatment during pregnancy and its consequences on pregnancy and fetus outcome.

Impact of intravenous lipid emulsion infusion on the stratum corneum barrier function in patients receiving parenteral nutrition.

The importance of the lipid matrix of stratum corneum (SC) in epidermal barrier function is well documented. Intravenous lipid emulsions (ILE) provide essential fatty acids (EFAs), main components of the SC lipid matrix. The objective of this study was to investigate the influence of ILE upon SC barrier function. The skin barrier was assessed by measuring transepidermal water loss (TEWL). Patients receiving lipid-containing parenteral nutrition (LCPN) were compared to patients receiving lipid-free PN (LFPN). In addition, a before/after LCPN introduction study was set up to limit the influence of inter-individual variability. Twenty-six patients receiving LCPN and seven patients receiving LFPN were included. Median age was not significantly different between the two groups. The TEWL of the LCPN group (9.05 g/m2/h) was significantly lower than the TEWL of the LFPN group (12.1 g/m2/h; Wilcoxon test: p = 0.016). The relative variation of TEWL before and after ILE treatment of 5 studied patients was 21.29 ± 10.28 %. ILE improve epidermal barrier function when compared to lipid-free parenteral treatments. Results of the before/after study confirm this conclusion and the usefulness of ILE intake for preventing excessive TEWL. SC barrier function improvement could be a choice criterion between the different ILE generations, in particular in burn patients and premature neonates.

[Factors predicting mortality during an outbreak of Legionnaire's disease in the north of France]. / Epidémie de légionellose dans le Pas-de-Calais (2003--2004): analyse descriptive et facteurs prédictifs d'une évolution défavorable.

Between November 2003 and January 2004 in the North of France a large outbreak of legionnaire's disease affected 85 patients. The clinical, biological and radiological characteristics of the patients were investigated to determine factors associated with mortality. Two populations were defined and compared: patients who died within 28 days and those who survived. Eighty-five patients were included in this study. The median age was 75 years. The median fever was 39.3 +/- 0.1 degrees. Fifteen patients (17.6%) had at least 3 underlying co-morbidities. Cough, dyspnoea, confusion and diarrhoea were found in respectively 46, 68, 47, and 15% of the patients. The median of urea was 0.7 +/- 0.05 g/L, creatinine 16 +/- 1.5 mg/L, CRP 332 +/- 15 mg/L. On the chest X-ray, lung infiltrates were present in 64% and multilobar in 40%. The overall mortality rate was 21%. In univariate analysis, diabetes mellitus, dyspnoea, urea>0.90 g/l and CRP>350 mg/l were predictive factors of mortality. In multivariate analysis, diabetes mellitus, urea>0.90 g/l, and bilateral infiltrates on chest X ray were retained as independent risk factors for death.

[Functional exercise testing in idiopathic inflammatory myopathies with pulmonary involvement]. / Intérêt de l'épreuve fonctionnelle d'exercice au cours des myopathies inflammatoires avec atteinte pulmonaire.

INTRODUCTION: Dyspnoea occurring during inflammatory myopathy associated with interstitial lung disease (ILD) can be ascribed to several physiopathological pathways. The purpose of this study was to analyse cardiopulmonary exercise testing (CPET) abnormalities in these patients in order to precise mechanisms responsible for decreased aerobic capacity. METHODS: Ten patients (52 +/- 12 years) were diagnosed as having inflammatory myopathy with interstitial lung disease. Exercise dyspnoea was found in 9 patients. All of them had a restrictive pattern associated to and impairment of the transfer factor for carbon monoxide. CPET was performed with a bicycle ergometer using a standard protocol of incremental increasing work load. RESULTS: Two patients had a normal exercise capacity while eight patients had abnormal VO2 associated with hyperventilation, abnormal gas exchange, as well as and abnormal dead space. Five patients also exhibited decreased oxygen pulse (<80% expected value) at peak exercise; 4 out of 5 had persistence of ventilatory reserve. In addition DeltaFC/DeltaVO2 was increased (>50) in 7 cases. CONCLUSION: CPET provides useful information in the understanding of mechanisms of dyspnoea and might be an effective tool in treatment decision making: in patients with inflammatory myopathy and associated ILD abnormal oxygen pulse may reflect cardiac disorder or muscular abnormalities (inflammatory or steroid myopathy).

[Langerhans cell histiocytosis and sclerosing cholangitis in adults]. / Association histiocytose pulmonaire langerhansienne et cholangite sclerosante de l'adulte.

INTRODUCTION: Langerhans cell histiocytosis and sclerosing cholangitis are two rare diseases that are frequently linked in children, but very rarely so in adults. CASE REPORT: A 40 year old woman with a 17 year history of Langerhans cell histiocytosis with chronic respiratory failure and diabetes insipidus presented with cholestatic jaundice whilst being assessed for lung transplantation. Pathological examination demonstrated sclerosing cholangitis. No Langerhans histiocytosis lesions were found in the liver or the biliary tract. Plans for pulmonary and hepatic transplantation were abandoned after cerebral involvement was detected, and the patient died of acute hepatic failure. CONCLUSION: This case underlines the need to monitor liver function in adult patients with disseminated Langerhans histiocytosis associated in adults, as coexisting sclerosing cholangitis is associated with a poor prognosis.

[The anti-synthetase syndrome]. / Le syndrome des anti-synthétases.

The anti-synthetase syndrome comprises the association of an inflammatory myopathy (polymyositis, dermatomyositis), interstitial pneumonitis, skin lesions characteristic of "mechanics hands", Raynaud's phenomena, inflammatory polyarthritis and, at the biological level, antinuclear antibodies known as anti-synthetases. We report our observations of two patients, one with a typical anti-synthetase syndrome and one with an incomplete form. Two men aged 49 and 47 presented with increasing dyspnoea upon effort, muscular weakness, arthralgia, bilateral pulmonary crackles and, in the first case, typical hairless skin lesions. In both cases the chest x-rays and CT scans confirmed the presence of interstitial lesions, predominantly in the lower lobes. Lung function tests showed a restrictive pattern with reduced gas transfer. At the biological level both patients presented an inflammatory picture with elevated muscle enzymes and anti-Jo-1 antibodies. Immuno-suppressive treatment with cortico-steroids and cyclophosphamide lead to a symptomatic improvement, regression of the radiological changes and improvement in the measurements of pulmonary function.

Cell and cytokine profiles in nasal secretions from patients with nasal polyposis: effects of topical steroids and surgical treatment.

BACKGROUND: Nasal polyposis (NP), a chronic inflammatory disease of the paranasal sinus mucosa, is frequently associated with asthma. Previous reports showed that surgical treatment for nasal polyps may influence asthma evolution. We hypothesized that sinus surgery may alter the cytokine network in nasal secretions. METHODS: We evaluated the characteristics (cells and mediators) of nasal lavages in nine patients with untreated NP (group A), 17 patients treated with topical steroids (group B), 21 patients treated by nasal surgery endonasal ethmoidectomy associated with topical steroids (group C), and 12 healthy subjects (controls). RESULTS: Percentages of both eosinophils and neutrophils were higher in NP patients than in controls. Percentages of eosinophils and interleukin-5 (IL-5) level were higher in group A than in group C and controls. There was a positive correlation between IL-5 and eosinophils. In marked contrast, IL-8, IL-10, and IL-1beta levels were significantly higher in group C than in groups A and B and controls; TNF-alpha concentration was significantly lower in group C than in groups A and B and controls; and there was a negative correlation between IL-10 and TNF-alpha. The percentage of eosinophils was higher in asthmatic patients with NP than in nonasthmatic patients. In addition, in group C, asthmatic patients also had a significantly higher level of IL-10 than nonasthmatic patients. CONCLUSIONS: Our study demonstrates that percentages of eosinophils and neutrophils, and IL-5 level were increased in nasal secretions from untreated patients with NP. Topical steroid treatment is associated with a decrease of inflammatory cells and mediators. In marked contrast, nasal surgery is associated with marked changes, in cytokine profile in nasal secretions, that are clearly different from those of controls and topical steroid-treated NP patients.

[Biological manifestations of sarcoidosis]. / Manifestations biologiques au cours de la sarcoïdose.

Sarcoidosis is a multisystem granulomatous disease of unknown origin. No single biological marker allows definitive diagnosis of sarcoidosis or may accurately predict the disease prognosis. However, some biological markers are helpful tools as diagnostic aids and disease activity markers. At the blood level, lymphopenia with CD4 depletion, elevated levels of serum-angiotensin converting enzyme, lyzozyme, beta 2 microglobulin and disturbed calcium metabolism resulting in hypercalcemia and hypercalciuria can help guide diagnosis. Lymphocytic alveolitis with a high CD4/CD8 ratio in bronchoalveolar lavage fluid is highly suggestive of the disease. A wide range of new biological markers are proposed but their pronostic significance is still controversial. In clinical practice, biological markers may help in monitoring treated patients with sarcoidisis.

Interstitial lung diseases in collagen vascular diseases.

In this review, a clinical update is presented of the most important collagen vascular diseases (CVDs) and the different types of interstitial lung disease (ILD) encountered in these CVDs. These CVDs represent a heterogenous group of immunologically mediated inflammatory disorders with a large variety of affected organs besides the lungs. The frequency, clinical presentation, prognosis and response to therapy vary depending on the histological pattern (usual interstitial pneumonia, desquamative interstitial pneumonia, organising pneumonia, diffuse alveolar damage, nodular lesions, etc.), as well as on the underlying CVD (scleroderma, rheumatoid arthritis, systemic lupus erythematosus, dermatopolymyositis, Sjogren's syndrome or mixed connective tissue disease). The diagnosis of most of these CVDs is based on a number of criteria; in several of these, however, lung involvement is not part of the diagnostic criteria. In addition, there may be overlaps between several of these CVDs. Optimal treatment varies depending on the type of collagen vascular disease and the presence of interstitial lung disease, although in many cases, a combination of corticosteroids and cytostatic drugs are given.

[The common mucosal immune system in respiratory disease]. / Le système immunitaire muqueux commun en pathologie respiratoire.

The principal function of the mucosal immune system is to protect the mucosa from exogenous aggression. It also involves a lymphocyte recirculation phenomenon allowing activated lymphocytes to migrate to the aggressed site, for example the bronchi, and to recirculate and colonize other sites of the mucosal immune system. In asthma, analysis of the other sites of the common mucosal immune system demonstrates asthma-like inflammatory reactions in the accessory salivary glands and the gut: lymphocyte infiltrate, mast cell activation, thickening of the basal membrane, accumulation and activation of eosinophils (gut), activation of endothelial cells expressing ICAM-1. Lymphocyte, eosinophil and mast cell infiltration is observed in the digestive tract as well as increased expression of IL-3, IL-5 and GM-CSF. The similarity of the anomalies observed in BALT and GALT tissues would suggest the entire mucosal immune system is implicated in asthma.

Increased frequency of asymptomatic bronchial hyperresponsiveness in nonasthmatic patients with food allergy.

Subclinical inflammation in gut mucosa has been demonstrated in bronchial asthma suggesting the whole mucosal system is involved in allergic diseases. The presence of subclinical bronchial involvement was assessed by nonspecific bronchial hyperresponsiveness (BHR) in nonasthmatic patients with food allergy (FA). BHR was studied in 35 patients with various manifestations of FA without food-induced asthma. Sixteen had a previous history of asthma and/or rhinitis to aeroallergens (group A), whereas 19 patients (group B) did not. BHR was defined by a provocative dose causing a 20% fall in forced expiratory volume in one second of (PC20) <8 mg.mL(-1) of methacholine. Asymptomatic BHR occurred frequently in nonasthmatic patients with FA (10 of 19, 53%); this did not significantly differ from patients with FA and a previous history of asthma and/or rhinitis to aeroallergens (13 of 16, 81%). PC20 was significantly lower in group A (1.84+/-0.53 mg.mL(-1)) than in group B (3.35+/-0.74 mg.mL(-1); p<0.05). The number of patients with positive skin tests to aeroallergens was similar between groups. Sequential evaluation, performed 1 year after initial evaluation, in 7 nonasthmatic patients (group B) demonstrated a similar level of BHR. The present study demonstrated that BHR is a frequent finding in nonasthmatic patients with food allergy which may be due, at least in part, to a subclinical inflammatory process in the bronchi.