Air travel in women with lymphangioleiomyomatosis.
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BACKGROUND AND OBJECTIVE: The safety of air travel in patients with pneumothorax-prone pulmonary diseases, such as lymphangioleiomyomatosis (LAM), has not been studied to any great extent. A questionnaire-based evaluation of air travel in patients with LAM was conducted to determine experiences aboard commercial aircraft. METHODS: A survey was sent to women listed in the US LAM Foundation registry (n = 389) and the UK LAM Action registry (n = 59) to assess air travel, including problems occurring during flight. Women reporting a pneumothorax in flight were followed up to ascertain further details about the incident. RESULTS: 327 (73%) women completed the survey. 308 women answered the travel section, of whom 276 (90%) had "ever" travelled by aeroplane for a total of 454 flights. 95 (35%) women had been advised by their doctor to avoid air travel. Adverse events reported included shortness of breath (14%), pneumothorax (2%, 8/10 confirmed by chest radiograph), nausea or dizziness (8%), chest pain (12%), unusual fatigue (11%), oxygen desaturation (8%), headache (9%), blue hands (2%), haemoptysis (0.4%) and anxiety (22%). 5 of 10 patients with pneumothorax had symptoms that began before the flight: 2 occurred during cruising altitude, 2 soon after landing and 1 not known. The main symptoms were severe chest pain and shortness of breath. DISCUSSION AND CONCLUSION: Adverse effects occurred during air travel in patients with LAM, particularly dyspnoea and chest pain. Hypoxaemia and pneumothorax were reported. The decision to travel should be individualised; patients with unexplained shortness of breath or chest pain before scheduled flights should not board. Patients with borderline oxygen saturations on the ground should be evaluated for supplemental oxygen therapy during flight. Although many women had been advised not to travel by air, most travelled without the occurrence of serious adverse effects. (+info)
Lymphangioleiomyomatosis.
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BACKGROUND: Lymphangioleiomyomatosis (LAM) is a rare disease that is characterized by proliferation of abnormal smooth muscle-like cells (LAM cells), which leads to the formation of lung cysts, fluid-filled cystic structures in the axial lymphatics, and abdominal tumors. It primarily affects women. METHODS: The authors present a review of large series, registries, and protocols to highlight the prevalence, pathology, clinical features, diagnosis, and treatment options for patients with LAM. RESULTS: LAM commonly presents with progressive breathlessness or with recurrent pneumothorax, chylothorax, or sudden abdominal hemorrhage. Computed tomography (CT) scans show numerous thin-walled cysts throughout the lungs, abdominal angiomyolipomas, and lymphangioleiomyomas. Pulmonary function tests show decreased forced expiratory volume in 1 second (FEV1) and diffusion capacity for carbon monoxide (DLCO). Exercise testing shows gas-exchange abnormalities, ventilatory limitation, and hypoxemia that may occur with near-normal lung function. CONCLUSIONS: No effective treatment currently exists for this progressive disorder. However, recent progress in cancer and smooth muscle cell biology and a better understanding of the factors regulating angiogenesis and lymphangiogenesis may provide a foundation for the development of new therapeutic strategies. (+info)
A pregnant woman with complications of lymphangioleiomyomatosis and idiopathic thrombocytopenic purpura.
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A pregnant 26-year-old woman developed hemosputum, dyspnea and pneumothorax. Lymphangioleiomyomatosis was suspected based on multiple cystic lesions on chest computed tomography. Additionally, moderate thrombocytopenia occurred during the last trimester. Hyperplasia of megakaryocytes in a bone marrow specimen and a high serum titer of platelet-associated IgG led to a diagnosis of idiopathic thrombocytopenic purpura. High-dose intravenous gammaglobulin promptly restored her platelet count, and the patient successfully gave birth to a healthy baby by cesarean section. After delivery, lymphangioleiomyomatosis was diagnosed by lung biopsy that was obtained during a video-assisted thoracoscopic abscission for recurrent pneumothorax. Underlying lymphangioleiomyomatosis and idiopathic thrombocytopenic purpura may be obviated by pregnancy. (+info)
Molecular pathogenesis of lymphangioleiomyomatosis: lessons learned from orphans.
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Lymphangioleiomyomatosis (LAM) is a rare progressive cystic lung disease affecting young women. The pivotal observation that LAM occurs both spontaneously and as part of the tuberous sclerosis complex (TSC) led to the hypothesis that these disorders share common genetic and pathogenetic mechanisms. In this review we describe the evolution of our understanding of the molecular and cellular basis of LAM and TSC, beginning with the discovery of the TSC1 and TSC2 genes and the demonstration of their involvement in sporadic (non-TSC) LAM. This was followed by rapid delineation of the signaling pathways in Drosophila melanogaster with confirmation in mice and humans. This knowledge served as the foundation for novel therapeutic approaches that are currently being used in human clinical trials. (+info)
Sporadic lymphangioleiomyomatosis and tuberous sclerosis complex with lymphangioleiomyomatosis: comparison of CT features.
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PURPOSE: To retrospectively compare the frequencies of computed tomographic (CT) findings in patients with lymphangioleiomyomatosis (LAM) and patients with tuberous sclerosis complex (TSC) and LAM. MATERIALS AND METHODS: Institutional review board approval and informed consent were obtained for the HIPAA-compliant study. In 256 patients with LAM (mean age, 44 years) and 67 patients with TSC/LAM (mean age, 40 years), CT scans of the chest, abdomen, and pelvis were reviewed by a single radiologist. The fraction of lung involvement with cysts was estimated from high-spatial-resolution CT scans. Other findings assessed included noncalcified pulmonary nodules, pleural effusion, thoracic duct dilatation, hepatic and renal angiomyolipomas (AMLs), lymphangioleiomyoma (LALM), ascites, nephrectomy, and renal embolization. Confidence intervals and hypothesis tests of differences in frequencies, comparison of age quartiles, RIDIT analysis, analysis of variance, and correlation coefficients were used in the statistical analysis. RESULTS: Patients with LAM had more extensive lung involvement (RIDIT score, 0.36) and higher frequency of LALM (29% vs 9%, P<.001), thoracic duct dilatation (4% vs 0, P=.3), pleural effusion (12% vs 6%, P=.2), or ascites (10% vs 6%, P=.3). Patients with TSC/LAM had higher frequency of noncalcified pulmonary nodules (12% vs 1%, P<.01), hepatic (33% vs 2%, P<.001) and renal (93% vs 32%, P<.001) AMLs, nephrectomy (25% vs 7%, P<.001), or renal artery embolization (9% vs 2%, P<.05). CONCLUSION: The extent of lung disease is greater in LAM than TSC/LAM. Hepatic and renal AMLs and noncalcified lung nodules are more common in TSC/LAM, while lymphatic involvement-thoracic duct dilatation, chylous pleural effusion, ascites, and LALM-is more common in LAM. (+info)
Oral findings in 58 adults with tuberous sclerosis complex.
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BACKGROUND: Gingival fibromas and dental pitting are among the diagnostic criteria for tuberous sclerosis complex (TSC). OBJECTIVE: Our goal was to document the oral findings in 58 adult patients with TSC. RESULTS: Forty patients (69%) had oral fibromas, appearing mostly on the attached or interdental gingiva. Other oral mucosal sites with fibromas included buccal and labial mucosa, the superior labial frenulum, palate, and tongue. In all, 56 patients (97%) had multiple dental enamel pits. LIMITATIONS: This case series comprised predominantly adult women with TSC and lymphangioleiomyomatosis. CONCLUSIONS: Oral fibromas in TSC are mostly, but not exclusively, gingival. Dental pits are present in nearly all patients. The multiple oral papules in TSC may appear similar to those observed in Cowden syndrome, Birt-Hogg-Dube syndrome, and rarely in multiple endocrine neoplasia type 1. (+info)
Identification of the benign mesenchymal tumor gene HMGA2 in lymphangiomyomatosis.
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The normal expression pattern of HMGA2, an architectural transcription factor, is primarily restricted to cells of the developing mesenchyme before their overt differentiation during organogenesis. A detailed in situ hybridization analysis showed that the undifferentiated mesoderm of the embryonic lung expressed Hmga2 but it was not expressed in the newborn or adult lung. Previously, HMGA2 was shown to be misexpressed in a number of benign, differentiated mesenchymal tumors including lipomas, uterine leiomyomas, and pulmonary chondroid hamartomas. Here, we show that HMGA2 is misexpressed in pulmonary lymphangiomyomatosis (LAM), a severe disorder of unknown etiology consisting of lymphatic smooth muscle cell proliferation that results in the obstruction of airways, lymphatics, and vessels. Immunohistochemistry was done with antibodies to HMGA2 and revealed expression in lung tissue samples obtained from 21 patients with LAM. In contrast, HMGA2 was not expressed in sections of normal adult lung or other proliferative interstitial lung diseases, indicating that the expression of HMGA2 in LAM represents aberrant gene activation and is not due solely to an increase in cellular proliferation. In vivo studies in transgenic mice show that misexpression of HMGA2 in smooth muscle cells resulted in increased proliferation of these cells in the lung surrounding the epithelial cells. Therefore, similar to the other mesenchymal neoplasms, HMGA2 misexpression in the smooth muscle cell leads to abnormal proliferation and LAM tumorigenesis. These results suggest that HMGA2 plays a central role in the pathogenesis of LAM and is a potential candidate as a therapeutic target. (+info)
Genetic and morphologic determinants of pneumothorax in lymphangioleiomyomatosis.
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Lymphangioleiomyomatosis, a multisystem disease affecting women, is characterized by proliferation of abnormal smooth muscle-like cells in the lungs, leading to cystic destruction of the parenchyma and recurrent pneumothoraces. Clinical characteristics of lymphangioleiomyomatosis patients were analyzed to determine the relationship of pneumothoraces to disease progression. Patients were genotyped for polymorphisms in genes of extracellular matrix proteins collagen, elastin, and matrix metalloproteinase-1 to assess their association with pneumothoraces. Clinical data and polymorphisms in the genes for types I and III collagen, elastin, and matrix metalloproteinase-1 were compared with the prevalence of pneumothorax. Of 227 patients, 57% reported having had at least one pneumothorax. Cyst size on high-resolution computed tomography scans was associated with pneumothorax; patients with a history of pneumothorax were more likely to have larger cysts than patients who had no pneumothoraces. In patients with mild disease, those with a history of pneumothorax had a faster rate of decline in forced expiratory volume in 1 s (FEV(1); P = 0.001, adjusted for age) than those without. Genotype frequencies differed between patients with and without pneumothorax for polymorphisms in the types I and III collagen and matrix metalloproteinase-1 genes. Larger cysts may predispose lymphangioleiomyomatosis patients to pneumothorax, which, in early stages of disease, correlates with a more rapid rate of decline in FEV(1). Polymorphisms in types I and III collagen and matrix metalloproteinase-1 genes may cause differences in lung extracellular matrix that result in greater susceptibility to pneumothorax. (+info)