Lung function in Birt-Hogg-Dubé syndrome: a retrospective analysis of 96 patients.

BACKGROUND: Birt-Hogg-Dubé syndrome (BHD) is a rare autosomal dominant disorder caused by mutations in the FLCN gene coding for folliculin. Its clinical expression includes cutaneous fibrofolliculomas, renal tumors, multiple pulmonary cysts, and recurrent spontaneous pneumothoraces. Data on lung function in BHD are scarce and it is not known whether lung function declines over time. We retrospectively assessed lung function at baseline and during follow-up in 96 patients with BHD. RESULTS: Ninety-five percent of BHD patients had multiple pulmonary cysts on computed tomography and 59% had experienced at least one pneumothorax. Mean values of forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), FEV1/FVC ratio, and total lung capacity were normal at baseline. Mean (standard deviation) residual volume (RV) was moderately increased to 116 (36) %pred at baseline, and RV was elevated > 120%pred in 41% of cases. Mean (standard deviation) carbon monoxide transfer factor (DLco) was moderately decreased to 85 (18) %pred at baseline, and DLco was decreased < 80%pred in 33% of cases. When adjusted for age, gender, smoking and history of pleurodesis, lung function parameters did not significantly decline over a follow-up period of 6 years. CONCLUSIONS: Cystic lung disease in BHD does not affect respiratory function at baseline except for slightly increased RV and reduced DLco. No significant deterioration of lung function occurs in BHD over a follow-up period of 6 years.

Diffuse bronchiectasis and airflow obstruction in granulomatosis with polyangiitis.

Parenchymal lung nodes and diffuse intra-alveolar hemorrhage are the archetypal pulmonary manifestations of Granulomatosis with Polyangiitis (GPA). The occurrence of diffuse bronchiectasis and airflow obstruction during GPA is unusual. We report here 3 patients with GPA who developed diffuse bronchiectasis during follow-up. The airflow obstruction seemed then to evolve independently from the GPA itself and ultimately led to respiratory insufficiency. Bronchiectases promoted the occurrence of opportunistic infections, especially with atypical mycobacteria. (Sarcoidosis Vasc Diffuse Lung Dis 2018; 35: 81-84).

Prevalence of fecal incontinence in a cohort of systemic sclerosis patients within a regional referral network.

BACKGROUND: The prevalence of gastrointestinal involvement in systemic sclerosis is higher than 75%. The estimated prevalence of fecal incontinence varies from 22% to 77%, but suffers from recruitment bias and patient reluctance. Our goal was to evaluate the prevalence of fecal incontinence in systemic sclerosis, and to identify associated risk factors. METHODS: Patients were recruited in the referral systemic sclerosis network of the Lyon University Hospitals, using self-administered questionnaires including constipation, fecal incontinence and Bristol Stool scales, quality of life, anxiety and depression. The cohort was compared with the historical ORALIA cohort that established the prevalence of fecal incontinence in the general population of the Rhône-Alpes region (France). RESULTS: Seventy-seven patients were included (mean age: 60 years, range: 32-84), and 86% were female. These were compared to 153 ORALIA individuals matched for age and sex. Fecal incontinence was present in 38% of patients and 6% of the general population. A longer duration of systemic sclerosis was the only characteristic associated with fecal incontinence. Abnormal stool consistency was more frequent in patients with fecal incontinence. CONCLUSION: Fecal incontinence and abnormal stool consistency are common in systemic sclerosis and should be systematically addressed.

[Pulmonary lymphangioleiomyomatosis: From pathogenesis to management]. / Lymphangioléiomyomatose pulmonaire : de la physiopathologie à la prise en charge.

INTRODUCTION: Pulmonary lymphangioleiomyomatosis (LAM) is a rare disease affecting mainly young women. BACKGROUND: The respiratory manifestations are characterized by a progressive cystic destruction of the lung parenchyma. Extrapulmonary involvement includes benign renal tumours called angiomyolipomas and abdominal lymphatic masses called lymphangioleiomyomas. At the pathological level, the cellular proliferation found in LAM is in part due to the presence of mutations in the tumour suppressor genes TSC1 and TSC2 (Tuberous Sclerosis Complex). These mutations lead to the activation of the mTOR pathway, which is currently the main therapeutic target. mTOR inhibitors such as sirolimus or everolimus have shown a beneficial effect on the decline in pulmonary function and a reduction of angiomyolipoma size, but are necessary in only some patients. PERSPECTIVES: LAM cells have migratory properties mediated by the formation of new lymphatic vessels. They are also able to secrete metalloproteases, which enhance their invasiveness. Moreover, the expression of estrogen and progesterone receptors by LAM cells suggests a possible role for sex hormones in the pathogenesis of the disease. CONCLUSION: A better understanding of mTOR-independent mechanisms would allow the development of novel therapeutic approaches.

[Interstitial lung disease and anti-TNF-alpha therapy in rheumatoid arthritis: Two different patterns?]. / Pneumopathie interstitielle diffuse et anti-TNF-alpha dans la polyarthrite rhumatoïde : deux formes différentes ?

The first lung complications of anti-TNF-alpha therapy in rheumatoid arthritis (RA) that were reported were infections. Recently, interstitial lung disease (ILD) has been described as a consequence of this treatment. We report two cases of women treated with anti-TNF-alpha therapy for RA who both developed exacerbations of their preexisting ILD thought to be due to the treatment. In one case, this complication occurred 2 months after anti-TNF-alpha therapy, whereas the delay of occurrence was 26 months in the second case. Based on these two cases and on the first 40 observations in the literature, we hypothesize that ILD may be exacerbated according to two distinct patterns during anti-TNF-alpha treatment for RA, occurring early (most frequently) or late after treatment was started, with a mean of 4 and 26 months, respectively. Other features that may differ between these two presentations include the risk factors, the anti-TNF-alpha molecule used, the histopathological pattern, and the prognosis.

Isolated recurrent pleuritis revealing familial mediterranean Fever in adulthood.

Familial Mediterranean fever (FMF) is a genetic autoinflammatory disease especially affecting populations of Mediterranean origin with an autosomal recessive inheritance. The cardinal manifestations consist of short febrile and painful attacks of peritonitis, arthritis and pleuritis developing during childhood. We report the case of a 26-year-old man of Tunisian descent who had febrile episodes of right-sided pleuritis without any extrathoracic complaints. Disappearance of attacks with one dose of colchicine (1 mg/day) strengthened the presumptive diagnosis of atypical FMF, which was further confirmed by genetic testing identifying the homozygous mutation M694I/M694I of the MEFV gene.

[Urinary incontinence due to chronic cough in interstitial lung disease]. / Incontinence urinaire à la toux au cours des pneumopathies interstitielles diffuses.

INTRODUCTION: Urinary stress incontinence affects 10% to 30% of the female population and may have a major impact on psychosocial health. In interstitial lung disease, chronic cough may lead to development of urinary incontinence, but the prevalence and impact of this symptom are unknown. OBJECTIVES: To determine the rate and impact of urinary stress incontinence among women with chronic cough due to interstitial lung disease. METHODS: 28 female patients with chronic cough secondary to interstitial lung disease and 15 controls were evaluated by questionnaires to determine the prevalence of cough-related urinary incontinence, its severity, and its impact on quality of life. RESULTS: Cough-related urinary incontinence was present in 14/28 patients with interstitial lung disease and chronic cough (50%), but in only 1/15 controls (7%, p=0.005). On a 5-points quality of life scale, the median impact of urinary incontinence was 3 (minimum=1, maximal=5), and the median impact of chronic cough was 3.5. The majority of patients (64%) believed that incontinence was a natural phenomenon due to ageing, all were ashamed by this symptom and 79% were unable to mention it to their caring physician. Only one physician had previously addressed this issue. CONCLUSION: Cough-related urinary incontinence is common in patients with interstitial lung disease and is largely overlooked. It may significantly alter quality of life. A systematic questioning by the physician would allow to promptly refer these patients for appropriate therapeutic interventions, such as perineal training.

Persistent airflow obstruction in asthma of patients with Churg-Strauss syndrome and long-term follow-up.

BACKGROUND: Little is known about the long-term outcome of airflow obstruction in asthma of patients with Churg-Strauss syndrome (CSS). METHODS: We conducted a retrospective study of 24 consecutive patients (aged 41.1 +/- 13.5 years) with CSS in a single center. All had asthma (starting 8.1 +/- 9.5 years prior to the diagnosis of CSS), blood eosinophilia (6.1 +/- 4.4 x 10(9)/l) and systemic manifestations of CSS. Antineutrophil cytoplasmic antibodies were found in 7 of 22 tested patients. Seven patients had smoked (a mean of 10 pack-years). All patients received oral corticosteroids, 11 cyclophosphamide and 23 inhaled corticosteroids. RESULTS: Airflow obstruction was found in 14 patients (70%) at diagnosis, and in 11 of 22 patients (50%) at the time of the clinical remission of CSS. The mean postbronchodilator FEV1/FVC and FEV1 were 69 +/- 12% and 74 +/- 21% of predicted at diagnosis (n = 20); 71 +/- 10% and 92 +/- 19% of predicted at the clinical remission (n = 22); and 64 +/- 13% and 80 +/- 21% at last visit (n = 13), respectively. During follow-up, postbronchodilator FEV1 increased by 30 +/- 28% in six patients with FEV1/FVC < 70% despite inhaled therapy who received higher dose of oral corticosteroids. At last visit, 5 of 13 patients (38%) with more than 3 years of follow-up had persistent airflow obstruction as defined by postbronchodilator FEV1/FVC < 70% and FEV1 < 80% of predicted. CONCLUSION: Airflow obstruction due to uncontrolled asthma is present despite corticosteroids in many patients at diagnosis and at clinical remission of CSS, and during follow-up. It may be still partly reversible with increased oral corticosteroid treatment.

[Isolated pleurisy revealing ovarian hyperstimulation syndrome]. / Pleurésie isolée révélant un syndrome d'hyperstimulation ovarienne.

Ovarian hyperstimulation is a rare but serious iatrogenic complication following induction of ovulation cycles. Release of vasoactive substances by the stimulated ovaries leads to leakage of intravascular fluid into the extracellular and serous spaces due to enhanced capillary permeability. Pleural effusion is a classical finding in the most severe forms, often associated with ascitis and signs of hemoconcentration. We report the case of a women who presented pleural effusion as the sole inaugural sign of ovarian hyperstimulation.

Rhabdomyosarcoma arising in mediastinal teratoma in an adult man: a case report.

We report a case of rhabdomyosarcoma which occurred in a mediastinal teratoma in a 44-year-old man. Presentation symptoms were chest pain, hoarseness and a cough. Diagnosis was fortuitous, performed by the histological and immunohistochemical study of a mediastinal tumour biopsy specimen that showed embryonal carcinoma and yolk sac tumour components associated with the rhabdomyosarcoma. After cisplatin-based chemotherapy (bleomycin-etoposide-cisplatin), surgical resection of the residual mediastinal tumour was performed. Histological and immunohistochemical study of this tumour confirmed the presence of mature teratoma and embryonal rhabdomyosarcoma. Evolution was marked by a local extension of the mediastinal tumour, occurrence of multiple metastases and bone marrow involvement. The patient died 8 months after diagnosis despite chemotherapy and radiotherapy. A review of the literature reveals that the development of rhabdomyosarcoma in primary mediastinal teratomas is unusual in adults. The diagnostic, therapeutic and prognostic implications of such an association are reviewed.

Oligoclonal T-cells in blood and target tissues of patients with anti-Hu syndrome.

T-cell clones of unknown significance (TCUS), assessed by monoclonal or oligoclonal T-cell patterns in PCR-DGGE, were detected in blood of 7/9 patients with anti-Hu syndrome. Clonal patterns were also detected in 2/2 neoplastic lymph nodes, and in 2/2 inflamed dorsal root ganglia from three patients. Only some T-cell clones found in target tissues were also detected in blood or non-target tissues, and likely corresponded to TCUS. In one patient, an identical T-cell clone was found in both neoplastic lymph node tissue and dorsal root ganglia, but not in blood. Dorsal root-infiltrating lymphocytes were cytotoxic CD8(+) TIA-1(+) T-cells. They were often found in close contact to sensory neurons, most of which expressed MHC-1. Taken together, these data support a direct effector role of cytotoxic CD8(+) T-cells, the same clones being likely operative in sensory neuron damage and immune-mediated tumor growth control.

[Paraneoplastic intestinal pseudo-occlusion and sensory neuronopathy disclosing small-cell bronchial cancer]. / Pseudo-occlusion intestinale et neuronopathie sensitive paranéoplasiques révélatrices d'un cancer bronchique à petites cellules.

This report describes a case of paraneoplastic neurological syndrome associating a subacute sensory neuronopathy and an intestinal pseudo-obstruction in a 64-year old man with a small cell lung cancer. Various paraneoplastic neurological syndromes have been described in association with small cell lung cancer. In our patient anti-Hu antibodies were identified by indirect immunohistochemistry and western-blot analysis. This antibody constitutes an informative tool in assessing the paraneoplastic origin of neurologic symptoms when the etiological inquiry is negative. Its positivity is important in promoting the search for an underlying malignancy and should lead to repeat investigations if the first investigations are normal.