The first symptoms of LAM, such as shortness of breath during exercise, coughing and chest pain, usually occur between the ages of 25 and 35 years [1] [2]. Because LAM is rare and its onset insidiously, the symptoms may be misdiagnosed as asthma, pulmonary emphysema, chronic bronchitis, chronic obstructive pulmonary disease or sarcoidosis and the correct diagnosis may be delayed for several years [1] [3]. As the disease progresses, progressive dyspnea, pneumothorax, and chylothorax occur [4]. LAM can lead to chronic respiratory insufficiency. Other possible symptoms include chylous ascites, abdominal and thoracic lymphadenopathy and abdominal tumors including angiomyolipomas of the kidney and lymphangiomyomas [5]. TSC-LAM has symptoms of TSC.

• Pain

  History of paroxysmal nocturnal dyspnea, chest pain, syncope, and joint pain were absent. Patient did not give any history of receiving antitubercular therapy. She was nondiabetic and nonhypertensive. [jdrntruhs.org]

  Cysts near or on the surface of the lung (blebs) can rupture and, as air leaks from the lung into the chest cavity ( pneumothorax ), the lung or a part of the lung can collapse, causing pain. [medicinenet.com]

  When large, they may compress adjacent organs and cause symptoms that include back pain, abdominal pain, urinary frequency, constipation, and lower extremity edema [ 6 ]. [ajronline.org]

  We report a case of a 23-year-old woman who presented with diffuse, but increasing abdominal pain. Transabdominal ultrasound showed multiple cystic formations. [ncbi.nlm.nih.gov]

• Lymphadenopathy

  However, extrapulmonary manifestations also occur, including renal angiomyolipomas, retroperitoneal lymphangioleiomyomas and extrathoracic lymphadenopathy. [ncbi.nlm.nih.gov]

  (see Lymphadenopathy, [[Lymphadenopathy]]) Epidemiology : common Lymphangioleiomyomas (Lymphangiomyomas) Epidemiology : occur in 16-20% of cases Physiology : benign neoplasms of lymphatic vessels (PEComas) May Vary In Size Diurnally (and Decrease in [mdnxs.com]

  Lymphadenopathy. Radiologic DDx (of cysts): Eosinophilic granuloma - associated with smoking. Usual interstitial pneumonia (UIP). Emphysema. [librepathology.org]

• Collapse

  Lymphangioleiomyomatosis causes damage to lung tissue that results in such problems as inability of fully oxygenate blood, fluid in the lungs and collapsed lung. [my.clevelandclinic.org]

  If air continues to leak into the chest cavity, however, it may be necessary to re-expand the collapsed portion of the lung by removing the air that has leaked into the chest cavity. [medicinenet.com]

  In mild cases of partial collapse, the lung may reinflate by itself. In other cases, surgery is needed. Sometimes, the condition is chronic and the affected lung may collapse over and over again. Pneumothorax is relatively common in people with LAM. [betterhealth.vic.gov.au]

  If you have a pneumothorax (collapsed lung) or large or growing angiomyolipomas, you might need additional hospital treatment. [blf.org.uk]

• Fatigue

  George's Respiratory Questionnaire, SGRQ), dyspnoea (modified Medical Research Council dyspnoea scale, mMRC) and fatigue (Multidimensional Fatigue Inventory, MFI-20). [ncbi.nlm.nih.gov]

  Patients without a collapsed lung will also have shortness of breath and may suffer from other symptoms including frequent coughing, enlarged lymph nodes, wheezing and fatigue. [lung.org]

  Fatigue Risks Causes and Risk Factors of Lymphangioleiomyomatosis (LAM) LAM results from mutations, or changes, in two genes called TSC1 and TSC2. A hereditary form of the disease also occurs in patients who have tuberous sclerosis disease. [loyolamedicine.org]

• Lymphedema

  We report the case of a 45-year-old woman with sporadic LAM, successfully treated with sirolimus, in whom the first manifestation of the disease was chyloperitoneum and after three and nine years, respectively, lymphedema of the left lower extremity and [ncbi.nlm.nih.gov]

  […] duct wall invasion, lymphangioleiomyomaformation, chylous fluidcollections in the peritoneal, pleural, andpericardial spaces, chyloptysis, chylocolporrhea/chylometrorrhea, chyle leak from theumbilicus, chylous pulmonary congestion,and lower extremity lymphedema [journals.uair.arizona.edu]

  Kazakov, Giant angiofibromas in tuberous sclerosis complex: A possible role for localized lymphedema in their pathogenesis, Journal of the American Academy of Dermatology, 67, 6, (1319), (2012). Daniel F. Dilling, Emily R. Gilbert, Maria M. [doi.org]

  Less commonly patients can present with chest pain, pleural or pericardial effusion and lymphedema. [bib.irb.hr]

• Dyspnea

  There was significant improvement in dyspnea, spirometry, and arterial blood gas values. However, radiological features remained stationary with no deterioration. [jdrntruhs.org]

  A 41-year-old woman with pulmonary lymphangioleiomyomatosis presented with exertional dyspnea. A chest computed tomographic scan showed hyperinflation with diffuse cystic lesions throughout both lung fields. [ncbi.nlm.nih.gov]

  Abstract Lymphangioleiomyomatosis (LAM) is a rare cystic lung disease presenting with cough, dyspnea on exertion and recurrent pneumothorax. [pesquisa.bvsalud.org]

  The common symptom is shortness of breath (dyspnea) A multifocal neoplasm with perivascular epithelioid cell differentiation affecting almost exclusively females of child-bearing age. [icd9data.com]

• Pleural Effusion

  Chylous pleural effusion and ascites occasionally appear during the course of the disease. There are only a few reports on the cytologic findings in this disease. [ncbi.nlm.nih.gov]

  Obstruction of the lymphatic vessels by the excess muscle growth can lead to leakage of fluid into the chest cavity ( pleural effusion ). [medicinenet.com]

  Her chest radiograph was suggestive of bilateral extensive reticulonodular pattern with cystic changes [Figure 1], but there was no evidence of pneumothorax or pleural effusion. [jdrntruhs.org]

  Lymphatic obstruction can also result in chylous pleural effusions (Figure 11.3). Spontaneous pneumothorax occurs in 20{\%}. Importance LAM is a progressive lung disease with a poor prognosis that typically affects women of childbearing age. [mayoclinic.pure.elsevier.com]

• Cough

  Abstract Lymphangioleiomyomatosis (LAM) is a rare cystic lung disease presenting with cough, dyspnea on exertion and recurrent pneumothorax. [pesquisa.bvsalud.org]

  Occasionally, patients cough up small amounts of blood. The symptoms are caused by the excessive growth of the muscle cells around the airways, and blood and lymph vessels. [medicinenet.com]

  Sometimes cough, chest pain, and coughing up blood (hemoptysis) also occur. Symptoms may worsen during pregnancy. Sometimes the first indication of the disease is when a lung collapses (pneumothorax) for no apparent reason. [msdmanuals.com]

  A 32-year-old primigravida presented with cough and dyspnea at 16 weeks' gestation. Chest roentgenogram revealed a large pleural effusion and diffuse interstitial infiltrates. [ncbi.nlm.nih.gov]

• Hemoptysis

  Pneumothorax, chylous effusions and hemoptysis were frequent complications. [ncbi.nlm.nih.gov]

  Pneumothorax, chylous effusions, and hemoptysis are frequent complications. The roentgenographic appearance is characteristic although not. .. [doi.org]

• Sputum

  She was diagnosed with chyloptysis and chylous pulmonary congestion by sputum analysis. [ncbi.nlm.nih.gov]

  Initial diagnosis was based primarily on clinical signs and symptoms and treatment was started despite the negative result of the sputum microscopy for acid fast bacilli. [pesquisa.bvsalud.org]

  Coughing up blood-stained sputum or blood (hemoptysis) is less frequent. Course: LAM is generally progressive, leading to increasingly impaired lung function. The rate of development can vary considerably among patients. [medicinenet.com]

  Natural History, Complications and Prognosis Natural history Patients will have a history of [2] [11] [12] [13] : Dyspnea Bluish discoloration of lips ( cyanosis ) Cough Chest pain Weight loss Blood in sputum Headache Pain abdomen Complications Ascites [wikidoc.org]

• Abdominal Pain

  We report a case of a 23-year-old woman who presented with diffuse, but increasing abdominal pain. Transabdominal ultrasound showed multiple cystic formations. [ncbi.nlm.nih.gov]

  Almost all manifestations in these patients were acute abdominal pain or abdominal masses. [wjso.biomedcentral.com]

• Abdominal Distension

  […] pain and distension Incidental abdominal mass Infertility, abdominal distension Recurrent bilateral pneumothoraces Lymphangioleiomyoma size at presentation* 8.3 cm × 4.3 cm × 17.5 cm 3 cm × 1 cm (coronal view) 9 cm × 3.5 cm (sagittal view) 5.1 cm × 2.3 [mja.com.au]

  Lymphangioleiomyomas can occur in the abdomen, pelvis and retroperitoneum with correlated symptoms such as abdominal distension and nausea. In patients that have TSC, neurological symptoms are also common. [jtd.amegroups.com]

  Associated symptoms are nausea, abdominal distension, peripheral oedema and urinary symptoms [86]. [err.ersjournals.com]

  Symptoms associated with lymphangioleiomyomas are nausea, bloating, abdominal distension, peripheral oedema and urinary symptoms 23. [erj.ersjournals.com]

• Chest Pain

  Lung is the most common site of involvement, and patients usually present with dyspnea, chest pain, and cough. Chylous pleural effusion and ascites occasionally appear during the course of the disease. [ncbi.nlm.nih.gov]

  Due to an increase in frequency of her intermittent pleuritic chest pain, a CT thorax was organised by her GP which picked up a 4mm cyst in the right midzone of her lung. [imj.ie]

  Cysts near or on the surface of the lung (blebs) can rupture and, as air leaks from the lung into the chest cavity ( pneumothorax ), the lung or a part of the lung can collapse, causing pain. [medicinenet.com]

  History of paroxysmal nocturnal dyspnea, chest pain, syncope, and joint pain were absent. Patient did not give any history of receiving antitubercular therapy. She was nondiabetic and nonhypertensive. [jdrntruhs.org]

• Exertional Chest Pain

  The symptoms of LAM may include: Shortness of breath Breathlessness during physical exertion Chest pain Cough Coughing up viscous white sputum Coughing up blood (haemoptysis) Progressive worsening of symptoms over time. [betterhealth.vic.gov.au]

• Osteoporosis

  Postmenopausal patients and patients with reduced mobility should be tested for osteoporosis. [rarediseases.org]

• Shagreen Patch

  patch Forehead plaque Retinal hamartoma Laboratory Findings Pulmonary function tests are used to assess the lung damage caused by lymphangiomyomatosis. [wikidoc.org]

  Besides facial angiofibromas and shagreen patches over the back, no other physical signs such as those referable to the respiratory system were noted. Chest X-ray performed did not show any abnormality. [nature.com]

  Finally, signs consistent with TSC, such as facial angiofibromas, periungual fibromas, nail ridging and the shagreen patch, are seen in patients with TSC-LAM. [err.ersjournals.com]

  Angiogenesis in TSC Patients with TSC may present with skin lesions such as forehead fibrous plaques, facial angiofibromas, ungual fibromas and Shagreen patches, in addition to brain and other manifestations [ 40, 41 ]. [doi.org]

  Subungual fibromas, facial angiofibromas and shagreen patches are all detectable clinically but may be misdiagnosed or overlooked in milder cases, and hypomelanotic patches require examination under Woods (ultraviolet) light for reliable detection. [erj.ersjournals.com]

• Skin Rash

  She presented with many clinical manifestations, including fever, skin rash, proximal muscle weakness, dyspnea, dysphagia and hypereosinophilia. She was diagnosed with eosinophilic myositis by the pathologic study. [kiss.kstudy.com]

  Uncommon effects include transient rises in tests for liver function and blood urea nitrogen, abnormal respiratory movements, loss of hair, skin rashes, activation of Horner's syndrome, weight changes, and rarely agranulocytosis or haemolytic anaemia. [inchem.org]

  rash or diabetes insipidus. [doi.org]

• Suggestibility

  It mainly involves the lungs where, as its name suggests, lymphatics ( lymph ), blood vessels ( angio ), and airways are surrounded by smooth muscle ( leiomyo ) proliferation. [thorax.bmj.com]

  Her chest radiograph was suggestive of bilateral extensive reticulonodular pattern with cystic changes [Figure 1], but there was no evidence of pneumothorax or pleural effusion. [jdrntruhs.org]

  LAM mainly involves the lungs where, as its name suggests, lymphatic (lymph), blood vessel (angio), and airways are surrounded by smooth muscle (leiomyoma) proliferation. [ncbi.nlm.nih.gov]

  Recent reports suggest that VEGF-D levels have diagnostic utility in LAM patients. [pesquisa.bvsalud.org]

• Flank Pain

  We report the case of a 25-year-old woman who presented with abdominal and flank pain with two successive pregnancies and was diagnosed of giant bilateral renal AMLs and pulmonary LAM associated with TSC in the post-partum of her second pregnancy. [ncbi.nlm.nih.gov]

  Pain (see Flank Pain, [[Flank Pain]]) Hematuria (see Hematuria, [[Hematuria]]): risk of hemorrhage increases with size Renin-Dependent Hypertension (see Hypertension, [[Hypertension]]): may occur Renal Mass (see Renal Mass, [[Renal Mass]]): often with [mdnxs.com]

  Renal angiomyolipomas, although usually asymptomatic, can cause bleeding if they grow large (eg, > 4 cm), usually manifesting as hematuria or flank pain. [msdmanuals.com]

• Hematuria

  (see Hematuria, [[Hematuria]]): risk of hemorrhage increases with size Renin-Dependent Hypertension (see Hypertension, [[Hypertension]]): may occur Renal Mass (see Renal Mass, [[Renal Mass]]): often with areas of fat attenuation on CT Chyluria (see Chyluria [mdnxs.com]

  Renal angiomyolipomas, although usually asymptomatic, can cause bleeding if they grow large (eg, > 4 cm), usually manifesting as hematuria or flank pain. [msdmanuals.com]

  […] lesions exceed 3 to 4 cm, they may become symptomatic and increase the risk for aneurysms that can lead to hemorrhage. [19] Other complications of lymphangioleiomyomatosis (LAM) include the following: Hemoptysis Chylothorax Ascites Chyloptysis Chyluria Hematuria [emedicine.medscape.com]

• Kidney Failure

  Angiomyolipomas: Noncancerous tumors may grow in the liver or kidneys. These can cause pain, bleeding, or kidney failure. In a few people with LAM, discovery of these benign tumors outside the lungs is the first sign of LAM lung disease. [webmd.com]

  Symptoms of LAM may include: Abdominal bleeding Abdominal pain Acute kidney failure Breathing problems, such as shortness of breath Chest pains Coughing up blood Fainting Fatigue Fluid buildup in the abdomen, chest and pelvis (chylous ascites) Persistent [loyolamedicine.org]

• Vaginal Discharge

  Clinical manifestations of LAM are dyspnea, cough, chest pain, chyloptysis, chylothorax, hemoptysis [8], spontaneous pneumothorax [9], pleural effusion [10], chylous ascites, lymphangiomyoma masses, chylous vaginal discharge, chyluria, uterine fibroids [lungindia.com]

The physical examination is often nonspecific but may reveal evidence of pleural effusion, ascites, pericardial effusion or pneumothorax, if present. High-resolution computed tomography (HR-CT) is the most sensitive method for diagnosing LAM. The typical findings are diffuse round, thin-walled cysts of varying sizes evenly distributed in all lung fields [3]. Other imaging results depend on the affected structures. Pulmonary function testing may be normal or may show obstructive, restrictive, or mixed patterns [5]. An increase of serum vascular endothelial growth factor D (VEGF-D) greater than 800 mg/L is common [6] [7] [8]. A LAM diagnosis without lung biopsy can be made in patients with typical cystic changes on pulmonary HR-CT scanning and findings of tuberous sclerosis, angiomyolipoma, lymphangioleiomyoma, thoracic or abdominal chylous effusion or serum VEGF-D > 800 mg/L, otherwise, a lung biopsy may be necessary [9].

• Pericardial Effusion

  The physical examination is often nonspecific but may reveal evidence of pleural effusion, ascites, pericardial effusion or pneumothorax, if present. High-resolution computed tomography (HR-CT) is the most sensitive method for diagnosing LAM. [symptoma.com]

  Pleural effusion Pneumothorax Ground-glass opacities Pericardial effusion Chylothorax Mediastinal lymphadenopathy Dilated thoracic duct Cystic lymph nodal lesions Renal angiolipomas in 50% of cases. [wikidoc.org]

  Less commonly patients can present with chest pain, pleural or pericardial effusion and lymphedema. [bib.irb.hr]

  effusion Pneumoperitoneum Lymphedema Respiratory failure Osteoporosis Meningioma Ferrans VJ, Yu ZX, Nelson WK, et al. [emedicine.medscape.com]

  Other less frequent symptoms are hemoptysis, chylous pleural effusions, chylous ascites, pericardial effusion, pneumoperitoneum, acute abdomen, and lymphedema. [scielo.br]

• Atelectasis

  (see Rounded Atelectasis, [[Rounded Atelectasis]]) Epidemiology : case reports describe rounded atelectasis occurring in the setting of LAM-associated pneumothorax and chylothorax Small Airways Disease (see Obstructive Lung Disease, [[Obstructive Lung [mdnxs.com]

  The effusions may be large and may cause atelectasis, dyspnea, cough, and chest pain [ 7, 8 ]. [ajronline.org]

  Kishi K, Homma S, Miyamoto A, Kurosaki A, Motoi N, Kohno T, et al: Rounded atelectasis associated with pulmonary lymphangioleiomyomatosis. Intern Med 2005;44:625-627. [karger.com]

  Pulmonary lymphangioleiomyomatosis and rounded atelectasis. JBR-BTR. 2004;87(3):152-3. Finlay G. The LAM cell: what is it, where does it come from, and why does it grow? Am J Physiol Lung Cell Mol Physiol. 2004;286(4):L690-3. [malattierare.regione.veneto.it]

• Pneumoperitoneum

  2013 림프관평활근종증을 동반한 산모의 제왕절개술을 위한 마취관리-증례 보고- - 2013 Profound Hypotension after an Intradermal Injection of Indigo Carmine for Sentinel Node Mapping - 2013 Effects of high positive end-expiratory pressure on haemodynamics and cerebral oxygenation during pneumoperitoneum [medicine.gachon.ac.kr]

  ] : Dyspnea Bluish discoloration of lips ( cyanosis ) Cough Chest pain Weight loss Blood in sputum Headache Pain abdomen Complications Ascites Pleural effusion pneumothorax Chylothorax H emoptysis Chyloptysis Chyluria Haematuria Pericardial effusion Pneumoperitoneum [wikidoc.org]

  […] become symptomatic and increase the risk for aneurysms that can lead to hemorrhage. [19] Other complications of lymphangioleiomyomatosis (LAM) include the following: Hemoptysis Chylothorax Ascites Chyloptysis Chyluria Hematuria Pericardial effusion Pneumoperitoneum [emedicine.medscape.com]

  Other less frequent symptoms are hemoptysis, chylous pleural effusions, chylous ascites, pericardial effusion, pneumoperitoneum, acute abdomen, and lymphedema. [scielo.br]

• Pleural Effusion

  Chylous pleural effusion and ascites occasionally appear during the course of the disease. There are only a few reports on the cytologic findings in this disease. [ncbi.nlm.nih.gov]

  Obstruction of the lymphatic vessels by the excess muscle growth can lead to leakage of fluid into the chest cavity ( pleural effusion ). [medicinenet.com]

  Her chest radiograph was suggestive of bilateral extensive reticulonodular pattern with cystic changes [Figure 1], but there was no evidence of pneumothorax or pleural effusion. [jdrntruhs.org]

  Lymphatic obstruction can also result in chylous pleural effusions (Figure 11.3). Spontaneous pneumothorax occurs in 20{\%}. Importance LAM is a progressive lung disease with a poor prognosis that typically affects women of childbearing age. [mayoclinic.pure.elsevier.com]

General care depends on the manifestation and may include treatment of pleural effusions and ascites, and for airway disease bronchodilators and supplemental oxygen [10]. Sirolimus, an mTOR inhibitor, stabilizes lung function, reduces symptoms, the size of angiomyolipomas, lymphangioleiomyomas, and chylous effusions, and improves life quality [11] [12] [13] [14] [15] [16]. If lung function markedly declines, in some patients lung transplantation may be required [17].

Survival estimates vary widely. Sporadic LAM is generally more severe than TSC-LAM.

To date, the cause of LAM is not fully understood. LAM occurs sporadically (S-LAM) or as a complication of tuberous sclerosis (TSC-LAM) [18]. TSC is an autosomal dominant genetic disorder associated with development of hamartomas and dysplastic lesions in several organs.

Overall, the disease is very rare and the international frequency of LAM is unknown. TSC-LAM is present in up to 40% of women with tuberous sclerosis complex [19] [20].

The proliferation of abnormal cells leads to airflow obstruction, overdistention of distal air spaces, bullae, and the formation of pneumothoraces. Obstruction of lymphatics due to infiltration by smooth muscle cells may result in chylothorax, and chylous ascites.

No guidelines present.

Lymphangioleiomyomatosis (LAM) is a rare disease affecting lung, kidney, and axial lymphatics that occurs almost exclusively in women of reproductive age [5] [21]. LAM was first described in a patient affected by TSC who presented with bilateral spontaneous pneumothorax in 1918 [22] and the spontaneous form in a patient without TSC in 1937 [23]. The disorder is characterized by abnormal smooth muscle cell proliferation that results in functional obstruction of vessels, lymphatics, and airways.

Lymphangioleiomyomatosis (LAM) is a rare disease that usually affects women of childbearing age. It is characterized by an abnormal growth of cells, particularly of smooth muscle-like cells, in the lungs, lymphatic system and kidneys. There are two forms of the disorder -sporadic LAM (S-LAM) and TSC-LAM, which can be inherited with tuberous sclerosis complex.

Lymphangioleiomyomatosis may cause a wide variety of symptoms including progressive shortness of breath with exertion and recurrent episodes of collapsed lung, which are similar to those of other lung diseases such as asthma, emphysema, and bronchitis, thus the correct diagnosis is often delayed.

A high-resolution computed tomography (HRCT) chest scan, pulmonary function tests, a blood test for vascular endothelial growth factor D (VEGF-D) and in some cases a lung biopsy may be needed to provide an accurate diagnosis.

In some counties, the drug sirolimus (Rapamune) was approved to treat LAM. In addition, bronchodilators and supplemental oxygen may be necessary. Lung transplantation may be considered for patients with very advanced disease.

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