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

  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]

• 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]

  Often misdiagnosed as asthma or emphysema, most LAM sufferers experience shortness of breath, collapsed lung, chest pain, and fatigue. LAM is a progressive disease, and there is no known cure. [uabmedicine.org]

  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]

• 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]

  […] 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, and lower-extremity lymphedema [lungindia.com]

  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]

• Soft Tissue Mass

  Omental soft tissue mass lesion is seen with heterogeneous enhancement as well as peritoneal masses seen abutting the anterior abdominal wall. Malignant rather dense ascites; predominately peri-hepatic and peri-splenic. [radiopaedia.org]

  Detecting lymphangiomyomas as soft tissue masses of fat density on CT scanning can strengthen the diagnosis of LAM when a tissue biopsy has not been performed. [doi.org]

  Extrapulmonary features include lymph node masses, cystic soft tissue masses,26 27 and chylous ascites in up to a third of patients.1 25 Uterine fibroids (leiomyomas)8and renal angiomyolipomas28 29 are also seen; angiomyolipomas are often asymptomatic [thorax.bmj.com]

• Dyspnea

  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]

  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]

  PNEUMOTHORAX AND PLEURAL EFFUSION Pneumothorax was common and frequently required surgical intervention. [doi.org]

• Cough

  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]

  One woman experienced clinical resolution of her abdominal pain and distension but did not have confirmatory follow-up imaging due to financial constraints. [mja.com.au]

• Abdominal Distension

  In one woman, temporary cessation of everolimus resulted in recurrence of abdominal distension, requiring reinstitution of therapy. Lung function Lung function was abnormal in all five patients at presentation. [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]

  Often misdiagnosed as asthma or emphysema, most LAM sufferers experience shortness of breath, collapsed lung, chest pain, and fatigue. LAM is a progressive disease, and there is no known cure. [uabmedicine.org]

  A 28 years old female admitted to our hospital with complaint of dry cough, exertional dyspnoea and chest pain for last 2 years. [lungindia.com]

• 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

  Many cases of LAM are associated with osteoporosis, a condition characterized by progressive thinning of the bones. Causes The exact cause of LAM is not known. [rarediseases.org]

  Care for your bones Some women who have LAM may be at risk for osteoporosis if they have undergone permanent hormonal therapy such as oophorectomy or are receiving certain hormone therapy medicines. [nhlbi.nih.gov]

  The available treatment options include: Oxygen therapy Pulmonary rehabilitation Removal of air or fluid from lungs or abdomen to help you breathe better Surveillance and treatment of osteoporosis (weak bones) Standard vaccinations to prevent respiratory [foundation.chestnet.org]

  Grade: B; Quality: low; Benefit: substantial; Consensus: very good. 2) Those with osteoporosis should be treated the same as other patients with osteoporosis. [doi.org]

  […] 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 Lymphedema Respiratory failure Osteoporosis [wikidoc.org]

• Shagreen Patch

  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]

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

  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]

• 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]

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

  A major complication of them is hemorrhage that may present with flank pain or shock [ 6 ]. [ajronline.org]

• Hematuria

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

  (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. [merckmanuals.com]

  In some cases, they may cause flank pain, blood in the urine (hematuria) or bleeding into the abdomen (abdominal hemorrhaging). [rarediseases.org]

• Kidney Failure

  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]

  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]

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

  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]

  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]

  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

  ] : 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]

  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]

  […] 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]

  PNEUMOTHORAX AND PLEURAL EFFUSION Pneumothorax was common and frequently required surgical intervention. [doi.org]

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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