Screening for latent tuberculosis in anti-TNF-α candidate patients in a high tuberculosis incidence setting.

BACKGROUND: Screening for latent tuberculosis infection (LTBI) using a protocol comprising chest X-ray and tuberculin skin test (TST) interpreted with medical history, Sc1, reduces LTBI reactivation on treatment with anti-tumour necrosis factor-alpha (anti-TNF-α). In the district of Seine-Saint-Denis, France, where tuberculosis (TB) incidence ranges from 30 to >100/100 000 person-years, however, Sc1 might be insensitive as a screening tool. We adopted another protocol, Sc2, comprising Sc1 plus two additional tests: the QuantiFERON(®)-TB Gold In-Tube (QFT-GIT) and chest computed tomography (CT). METHODS: We screened 123 consecutive patients with inflammatory rheumatic diseases (IRDs), candidates for anti-TNF-α treatment, and evaluated the impact of Sc2 vs. Sc1 on the prescription of prophylactic anti-tuberculosis treatment. RESULTS: Sc2 led to a diagnosis of LTBI in 69 patients vs. 59 when using Sc1: eight were QFT-GIT-positive. Diagnosis was based on CT findings in two patients. QFT-GIT had higher diagnostic accuracy than TST, but no single diagnostic test could detect all patients at high risk for LTBI reactivation (respectively 30.2% and 37.5% of patients positive with only TST or QFT-GIT). CT detected TB sequelae in 3/46 rheumatoid arthritis patients who were negative to all tests. CONCLUSIONS: Testing with both TST and QFT-GIT seems the safest strategy for detecting LTBI in patients with IRD from populations with high incidence of TB. Systematic screening with CT warrants further evaluation.

[Pulmonary sarcoidosis imaging]. / Imagerie de la sarcoïdose pulmonaire.

Sarcoidosis is a juvenile systemic granulomatosis. Its polymorphic clinical presentation depends on its different localisations, thoracic and extrathoracic. The role of imaging is very important for all localisations; but for mediastinopulmonary involvement, which is the most frequent (>90% of cases), it plays a major role in detecting the disease, diagnosing it, its prognosis, decision-making regarding treatment of it and in the monitoring of its development. Standard radiography, which sometimes detects the disease, forms the basis for its four-stage prognostic classification. CT scanning enables the study of mediastinal and hilar lymphadenopathy and the study of parenchyma, making it possible to identify micronodules of lymphatic distributions, alveolar opacities, septal lines, ground-glass hyperintensities, nodules surrounded by a ring of satellite micronodules, peribronchovascular thickening; all potentially reversible lesions. Elsewhere, it highlights irreversible fibrous lesions: hilar peripheral linear opacities; septal linear opacities; bronchial distortion, honeycomb destruction or even perihilar fibrotic masses. Less frequently we can visualise bronchiolar or cystic involvement. Benign in most cases, the sarcoidosis prognosis becomes bleaker in the event of hemoptysis, Aspergillus colonisation or before the onset of pulmonary hypertension.

[MRI features of spinal neurosarcoidosis associed with cervical spondylosis]. / Myélopathie sarcoïdosique associée à un canal cervical rétréci : aspects IRM.

INTRODUCTION: Spinal neurosarcoidosis is rare and exceptionally inaugural. OBSERVATION: A 49-year-old African woman developed a progressive left Brown-Sequard syndrome. Magnetic resonance imaging (MRI) scans of the cervical spinal cord revealed an intramedullary lesion from C2 to T1 with intense pial enhancement after administration of contrast material associated with cervical spondylosis. The diagnostic of sarcoidosis was confirmed by liver biopsy which demonstrated noncaseating granulomas. CONCLUSIONS: MRI features of spinal neurosarcoidosis were reviewed by the authors with focus on differential diagnosis.

[Pathophysiological approach to infiltrative lung diseases on CT]. / Approche pathogénique de la sémiologie tomodensitométrique des pneumopathies infiltratives diffuses.

The analysis of HRCT findings of interstitial lung diseases frequently allows to predict the reversible nature of abnormalities, to recognize the involved components of the lung and to suggest the underlying pathophysiological mechanisms. Pathologic alterations in the anatomy of secondary pulmonary lobules include interlobular septal thickening or/and diseases with peripheral lobular distribution, centrilobular abnormalities, and panlobular abnormalities. Consolidations and ground glass opacities are better analyzed by taking into account the way lung responds to injury rather than anatomic distribution of lesions. The recognition of the topographic distribution of lesions and associated abnormalities, including airway diseases, pulmonary hypertension and embolus, diaphragmatic and pharyngeal dysfunctions, provides a better understanding of underlying disease mechanisms and allows a limited differential diagnosis.

[CT imaging features of pulmonary involvement in connective tissue disorders]. / Sémiologie tomodensitométrique de l'atteinte pulmonaire des connectivites.

Connective tissue disorders correspond to a heterogeneous group of inflammatory diseases characterized by abnormal immune system activity leading to connective tissue alterations in multiple parts of the body. In adults, connective tissue disorders include rheumatoid arthritis, progressive systemic sclerosis, Sjögren syndrome, systemic lupus erythematosus, dermatomyositis and polymyositis, ankylosing spondylitis, and mixed connective tissue disease. Broncho-pulmonary involvement may be variable with involvement of all anatomical components of the lung. Involvement of other intrathoracic structures (pleura, respiratory muscles, heart, rib cage) is frequent. The most specific manifestations include interstitial lung diseases and pulmonary hypertension. During follow-up, progressive respiratory diseases may occur due to the treatment, infections, pulmonary embolism or neoplasms.

[Combined apical emphysema and basal fibrosis syndrome (emphysema/fibrosis syndrome): CT imaging features and pulmonary function tests]. / Syndrome emphysème des sommets et fibrose pulmonaire des bases combinés (syndrome emphysème/fibrose): aspects tomodensitométriques et fonctionnels.

PURPOSE: To describe the high resolution CT (HRCT) imaging and functional features of the emphysema/fibrosis syndrome. PATIENTS AND METHODS: A total of 61 patients were included based on HRCT. We have quantified the extent of fibrosis and emphysema lesions and a combined score was calculated. The scores were correlated to pulmonary function test parameters and specific HRCT features were described. RESULTS: The emphysema and fibrosis scores correlated with functional parameters of obstruction and restriction respectively. The combined score correlated with the reduction in DLCO and degree of pulmonary hypertension. Three HRCT patterns were identified: progressive transition (n=23, 38%) with diffuse emphysema (centrilobular and/or bullous) and zone of transition between bullae and honeycombing; paraseptal emphysema (n=13, 21%) with predominant subpleural bullae of enlarging size at the bases; separate processes (n=14, 23%) with independent areas of fibrosis and emphysema. Eleven patients (18%) could not be classified. The HRCT imaging features changed based on TLC (p=0.04) and FEV1/FVC (p=0.01). CONCLUSION: The emphysema/fibrosis syndrome may be associated with different patterns on HRCT corresponding to specific profiles on pulmonary function tests.

Short- and long-term response to corticosteroid therapy in chronic beryllium disease.

Chronic beryllium disease (CBD) is a granulomatous disorder that affects the lung after exposure to beryllium. The present study reports short- and long-term evolution of granulomatous and fibrotic components in eight patients with severe CBD receiving corticosteroid therapy. Eight patients with confirmed CBD were studied at baseline, after initial corticosteroid treatment (4-12 months), at relapse and at the final visit. Beryllium exposure, Glu(69) (HLA-DPB1 genes coding for glutamate at position beta69) polymorphism, symptoms, pulmonary function tests (PFT), serum angiotensin-converting enzyme (SACE) and high-resolution computed tomography (HRCT) quantification of pulmonary lesions were analysed. The CBD patients were observed for a median (range) of 69 (20-180) months. After stopping beryllium exposure, corticosteroids improved symptoms and PFT (vital capacity +26%, diffusing capacity of the lung for carbon monoxide +15%), and decreased SACE level and active lesion HRCT score. In total, 18 clinical relapses occurred after the treatment was tapered and these were associated with SACE and active lesion HRCT score impairment. At the final visit, corticosteroids had completely stabilised all parameters including both HRCT scores of active lesions and fibrotic lesions in six out of eight patients. Corticosteroids were beneficial in chronic beryllium disease. They were effective in suppressing granulomatosis lesions in all cases and in stopping the evolution to pulmonary fibrosis in six out of eight patients.

[Interstitial lung disease in systemic sclerosis]. / Pneumopathie infiltrante diffuse de la sclérodermie systémique.

INTRODUCTION: Interstitial lung diseases (ILD) in systemic sclerosis (SSc) are mainly encountered in patients with diffuse disease although they may occur less frequently in patients with limited cutaneous disease. BACKGROUND: In SSc early detection of ILD should be achieved by high resolution computed tomography and pulmonary function tests, including measurement of DLCO. In total up to 75% of patients with SSc develop ILD but it is progressive in only a minority of patients. Unlike idiopathic ILD, SSc associated ILD corresponds to non-specific interstitial pneumonia rather than usual interstitial pneumonia in the majority of cases. This explains the better prognosis of SSc associated ILD compared with idiopathic ILD. Nevertheless ILD represents one of the two main causes of death in SSc. VIEWPOINT: The treatment of SSc associated ILD is not well established. Anti-fibrosing treatments have failed to demonstrate benefit and cyclophosphamide, which has been used for about 15 years in the treatment of this condition, has recently been evaluated in two prospective randomised studies which showed a significant but modest effect on respiratory function. CONCLUSION: A subgroup of patients with rapidly progressive ILD might benefit from pulsed intravenous cyclophosphamide combined with prednisone 15 mg daily, but this remains to be confirmed.

[Pulmonary metastases from endometrial stromal sarcoma may benefit from hormone therapy]. / Les métastases pulmonaires de sarcomes utérins peuvent bénéficier d'une hormonothérapie!

INTRODUCTION: Low grade endometrial stromal sarcoma (ESS) often expresses oestrogen (ER) and progesterone (PR) receptors, even in metastatic disease. These receptors may also be hormone dependent. CASE REPORT: Two years after the institution of oestrogen replacement therapy (HRT) a woman of 56 presented with haemoptysis which led to the discovery of multiple pulmonary nodules. Twelve years previously the patient had had a hysterectomy for a low grade endometrial stromal sarcoma, ER and PR positive. Surgical resection of the nodules on the right side confirmed the diagnosis of metastatic endometrial stromal sarcoma. The metastases expressed oestrogen and progesterone receptors. Three months after the withdrawal of HRT and treatment with an aromatase inhibitor (letrozole) the contralateral metastases had disappeared and this complete response was maintained for more than 2 years of follow-up. CONCLUSION: Care should be taken in the institution of HRT in a woman with a history of low grade ESS. Hormonal treatment with aromatase inhibitors may be considered in cases where ER and PR are expressed by the primary tumour and metastases, with possible benefits even in metastatic disease.

[Other malignant tumors of the pleura]. / Autres tumeurs pleurales malignes.

Malignant tumors of the pleura are most often diffuse, nethertheless they are sometimes localized. There is an overlap of the radiologic features of the benign and malignant pleural lesions. The differential diagnosis may be difficult, even on histological sample. Imaging allows the diagnosis of pleural involvement, suggests the malignity, guides percutaneous or thoracoscopic biopsies of the pleura, defines extent of the tumor and follows the course of the disease. We will describe the malignant pleural tumors: pleural metastases, pleural involvement of broncho-pulmonary cancer, of lymphoma and leukaemia. Then the rare pleural tumors will be described: malignant pleural fibroma, sarcoma, histiocytoma and hemangiopericytoma.

[Chronic beryllium disease: a model of interaction between environmental exposure and genetic predisposition. Pathogenesis and clinical features (Part 2)]. / Bérylliose pulmonaire chronique (2e partie). Pathogénie, expression clinique, prévention et législation.

INTRODUCTION: Chronic beryllium disease (CBD) is an occupational lung disease caused by the inhalation of beryllium dust, fumes or metallic salts. CURRENT DATA: Beryllium affects the lungs via particles deposited in the pulmonary alveoli. These are ingested by alveolar macrophages which act as antigen presenting cells to CD4+ T lymphocytes. T lymphocytes proliferate in response to beryllium antigens and combined with macrophages produce numerous epithelioid granulomas with the release of inflammatory cytokines (IFNgamma, IL-2, TNFalpha and IL6) and growth factors. Beryllium induces macrophage apoptosis which reduces its clearance from the lung which in turn contributes to the host's continual re-exposure and thus a chronic granulomatous disorder. Pulmonary granulomatous inflammation is the primary manifestation of CBD, but the disease occasionally involves other organs such as the liver, spleen, lymph nodes and bone marrow. The clinical, radiological, and histopathological features of CBD can be difficult to distinguish from sarcoidosis. The Beryllium lymphocyte proliferation test (BeLPT) demonstrates a beryllium specific immune response, confirms the diagnosis of CBD, and excludes sarcoidosis. CONCLUSIONS AND PERSPECTIVES: CBD provides a human model of pulmonary granulomatous disease produced by an occupational exposure, occurring more frequently in those with a genetic pre-disposition. It can be differentiated from sarcoidosis by specific immunological testing.

Is high-resolution computed tomography a reliable tool to predict the histopathological activity of pulmonary Langerhans cell histiocytosis?

High-resolution computed tomography (HRCT) has proved to be very useful in the diagnosis and follow-up of pulmonary Langerhans cell histiocytosis (PLCH), but the precise relationships between nodules and thin-wall cysts observed by HRCT, and granulomatous or cystic lesions present in lung tissue, remain to be established. The aim of this study was to compare quantitative data obtained by HRCT and those obtained by histopathological examination of corresponding lung tissue specimens in patients with biopsy-proven PLCH. The results demonstrated that the extent of nodular abnormalities was strongly correlated with the density of florid granulomatous lesions in lung tissue. A strong correlation was also found between the extent of cystic abnormalities and the density of cavitary lesions, but the latter included both still inflammatory cavitary granulomas and cicatricial fibrous cysts. Interestingly, small isolated florid granulomas were found in lung tissue from most patients with a predominant cystic CT scan pattern. Taken together, these results demonstrate that HRCT has to be considered with caution to evaluate the histopathological activity of PLCH. Patients presenting with predominant HRCT cystic abnormalities should benefit from a long-term follow-up. Because these patients are susceptible to developing severe respiratory insufficiency, they should also be considered for treatment as soon as an effective therapy for LCH is available.

[Diagnostic approach in diffuse infiltrative lung diseases]. / Approche diagnostique des pneumopathies infiltrantes diffuses.

Infiltrative lung diseases (ILD) include more than 130 diseases. Chronic and acute forms of ILD must be differentiated. In each group, cases with a known cause or with an unknown cause have to be individualized. For the physician, the distinctive sign of ILD is the evidence of diffuse pulmonary opacities on chest X rays or a suggestive pattern on pulmonary function tests. The diagnosis of chronic ILD depends on epidemiologic data ("a priori" probabilities), anamnestic informations, clinical and radiological (radiography and tomodensitometry) findings which make possible to consider a diagnosis of high probability in at least 60% of cases and reduce the gamut of hypothesis in the others. Other investigations (blood, endoscopy, broncho-alveolar lavage and sometimes surgical lung biopsy) lead to the final diagnosis. Most frequent chronic ILD are sarcoidosis, idiopathic pulmonary fibrosis and connective disease associated ILD. In case of acute ILD, diagnostic procedures depend on the severity of the disease and symptomatic treatment is urgent. The main lung lesion is either oedema or alveolitis. Main acute ILD are respectively cardiogenic oedema, lesional oedema, intra-alveolar hemorrhage, infectious ILD and acute eosinophilic pneumonia. The diagnostic approach depends on the presence of an initial orientation. Sometimes, several causes are associated.

Airway obstruction in bronchial sarcoidosis: outcome with treatment.

STUDY OBJECTIVE: Airway obstruction (AO) in sarcoidosis is reported to be associated with respiratory symptoms, increased morbidity, and an increased mortality risk. Because AO in sarcoidosis may result from several causes, the therapeutic benefit of corticosteroids is difficult to determine. The aim of this study was to evaluate the therapeutic response of AO attributable to sarcoid granulomas in the bronchial wall. PATIENTS: We selected 11 patients who had sarcoidosis with AO (defined as FEV(1)/vital capacity [VC] < 70%) associated with sarcoid granulomas on an endobronchial biopsy. Exclusion criteria were history of asthma, smoker or ex-smoker, stage 4 disease, evidence of extrinsic compression by enlarged lymph nodes, and localized endobronchial stenosis seen during fiberoptic bronchoscopy. INTERVENTIONS: We compared the results of pulmonary function tests and clinical, radiologic, and biological findings at baseline with those obtained at the time of the last pulmonary function tests available, between the sixth and 12th months of treatment. Eight patients took oral corticosteroids (20 to 60 mg/d initially), one received IV methylprednisolone pulses, another took oral hydroxychloroquine, and the last one received IM methotrexate. MEASUREMENTS AND RESULTS: With treatment, FEV(1) and FEV(1)/VC significantly improved in eight patients (72%), normalized in four patients, and was unchanged in the remaining three patients. The mean FEV(1) increased from 60.8 +/- 10.8% to 76 +/- 13.7% of the predicted value (p < 0.02). VC did not change significantly. FEV(1)/VC increased from 76.1 +/- 6.4% to 87.6 +/- 10.7% of the predicted value (p < 0.01). Dyspnea on exertion and other clinical findings were attenuated in 10 patients; the chest radiograph improved in 9 patients, and normalized in 5 patients. The mean serum angiotensin-converting enzyme level decreased from 112 +/- 48 to 58 +/- 40 IU/mL (p < 0.05), and normalized in four patients. CONCLUSION: The present study indicates that AO caused by sarcoid granulomas in the bronchial wall can be either partially or completely reversed by treatment with a concomitant attenuation of pulmonary symptoms.