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Dr Martin PPT Flipbook PDF
Dr Martin PPT
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LAM LYMPHANGIOLEIOMYOMATOSIS Rosa M. Estrada-Y-Martin, MD MSc CMQ FCCP Director, LAM/RLD Clinic McGovern Medical School -The University of Texas Health Science Center at Houston
OBJECTIVES • What is LAM and its manifestations • How to improve your health in general • Few words about sirulimus/everolimus
LYMPHANGIOLEIOMYOMATOSIS
• Lymph = Transporting liquid fat (chyle), antibodies and lymphocytes • angio = vessels • leiomyo = smooth muscle • matosis = disease process
LAM • Rare, slowly progressive tumor affecting the lungs and other organs • It is caused by infiltration of the lungs with smooth muscle-like cells which arise from unknown area in the body (LAM cells) • LAM cells spread via blood vessels and lymphatics (contain growth activating mutations in the tuberous sclerosis genes)
LAM • Smooth muscle-like cells (LAM cells) can infiltrate small airways called terminal bronchioles, causing obstruction which is believed to cause progressive dilatation of the distal airspaces leading to the formation of cysts
LAM • It is a slowly progressive lung disease that primarily affects women of reproductive age • Affects persons with tuberous sclerosis complex = TSC-LAM and “sporadic” form = S-LAM
LAM • LAM is caused by a mutation in either of the two tuberous sclerosis genes (TSC), TSC1 or TSC2 • TSC1 = autosomal-dominant affects skin, lung, kidneys and brain = TSC-LAM. All the cells in the body are affected with this gene mutation • TSC2 = S-LAM gene mutation is present only in LAM tumor cells (lungs, kidneys and lymph nodes) Only TSC2 have been reported in S-LAM
GENE MUTATION
TUMOR SUPPRESSORS
TSC1
TSC2
ENCODE LARGE PROTEINS CALLED HAMARTIN AND TUBERIN
DEFICIENCY OR MALFUNCTION CAUSE UP REGULATION OF mTOR CELLULAR PROLIFERATION, MIGRATION AND INVASION
INCREASES THE VASCULAR ENDOTHELIAL GROWTH FACTOR (VEGFs)
LAM • VEGF-D serum levels are elevated in 50% - 70% of persons with LAM (helps with diagnosis and prognosis) • Level > 800 pg/ml with typical chest CT findings practically confirms a LAM diagnosis
LAM • TSC-LAM affects > 30% of women with TSC and up to 10% - 15% of men with TSC • S-LAM 3 to 7 per million women • However, only 5 - 10% of persons with TSC-LAM develop symptoms
LAM • Average age at diagnosis is 35 yrs • TSC-LAM can be diagnosed earlier due to routine screening • Usual manifestations are shortness of breath, chronic cough, very rarely coughing up blood • Usually the diagnosis is suspected after the lung collapses (pneumothorax)
LAM when to suspect it • Young or middle-aged nonsmoking women with pneumothorax (lung collapse) • Persons with LAM can have kidney tumor called angiomyolipomas (AML) • Chylous pleural effusions or chylous fluid in the abdomen • Women with TSC • Unusual asthma or COPD presentations in women
LAM Follow up • Pulmonary function testing • Six minute walk • A word about Chest CT • Labs
Normal lung
LAM lung
Courtesy of Dr Sandra A. Oldham
LAM
LAM lungs numerous air cysts
Air cysts have very thin walls
Air cysts are distributed throughout both lungs
LAM lung The chest x-ray may look normal Really need to do a chest CT scan
LAM
Normal lungs
LAM
chest x-ray: right pneumothorax
LAM Management • Angiomyolipomas (AMLs) > 4 cm have the tendency to bleed (embolization or treatment with mTOR inhibitors is recommended) • Pleurodesis should be performed with the initial pneumothorax. The risk of recurrence is > 70%
Normal kidneys on CT scan
Normal kidneys
right angiomyolipoma
• Renal AML > 4 cm or pt with multiple tumors can spontaneously bleed ! hematuria and flank pain. Treatment should aim to conserve as much renal tissue as possible. • Small asymptomatic renal angiomyolipomas do not require treatment. Can be followed by US or CT.
LAM Management • Air travel is considered safe • Keep up with usual medical care and recommendations • Do not take “natural products” • Bronchodilators may be useful in some • If oxygen is needed use it all the time • Lung transplantation may be necessary
LAM Management • LAM is progressive, 50% will develop shortness of breath with exertion in 10 yrs, 20% will require oxygen • Women with S-LAM pre-menopausal and with high level of VEGF-D are at higher risk of progression • Pregnancy and use of estrogens also accelerate the disease
LAM Management • Stop smoking • Exercise and stay active • Become involved with LAM groups
LAM Management • Miles trial demonstrated that sirulimus in persons with LAM stabilized lung function, improved quality of life, and improved functional status. • Sirulimus is a mTOR inhibitor
SIROLIMUS • Sirolimus = Rapamune® • Anti-rejection medication after kidney transplant • Careful: allergic reactions, liver problems, lymphoma, skin cancer or family hx of skin cancer. • Avoid pregnancy
SIROLIMUS • Interaction with cholesterol or triglycerides medications, some antibiotics, BP, anti-seizure, antacids, HIV or HCV meds and St John’s wort • Do not crush, chew or split • Once a day • Check blood levels • Take the dose at the same time, with or without food • Do not take it with grapefruit
SIROLIMUS • Avoid live vaccines • Limit sunlight and UV light exposure. Cover your skin and use sunscreen • Side effects: serious allergic reactions, swelling of hands and feet, poor wound healing, increases risk of viral infections • Common side effects: high BP, diarrhea, headache, low platelet count, anemia, pain (stomach or joints)
everolimus • Everolimus - Zortress® • same side effects • twice daily • Both: acne, mouth sores and hair loss
LAM cells
TSC1-TSC2 mTOR up
mTOR inhibitors Sirolimus/Everolimus
LUNGS KIDNEYS