Chapter 168 - Lymphedema introduction Flashcards
Two types of lymphedema and causes
High-input failure = venous edema exceeding maximum transport capacity of lymphatic conduit
low-output failure = compromised lymphatic flow
Consequence of lymph stasis
protein and cellular metabolite build up in extracellular space –> osmotic pressure increas e–> increase hydraulic pressure
Accumulation of hyaluronan and glycoprotein in extracellular space –> increase fibroblast, keratinocyte and adipocyte –> collagen deposition
Clinical classification of lymphedema
Primary lymphedema
Secondary lymphedema
Primary lymphedema subclassification
Genetic: familial vs sporadic
Onset: congenital (at birth), praecox (at puberty), tarda (after age 35)
Epidemiology of primary lymphedema
1) female 2-10x more often
2) incidence peak age 12-16
3) 1/6000-10000 livebirth
Chance of bilateral lymphedema
25%
Congenital lymphedema type of transmission
Autosomal dominant
with sporadic penetrance
Association of congenital lymphedema with genetic chromosomal abnormalities and syndromes
1) Turners
2) Klinefelters
3) trisomy 21
4) Noonan’s
5) neurofibromatosis
6) yellow nail syndrome
7) intestinal lymphagiectasia
8) lymphagiomatosis (generalize lymphatic anomaly
9) AVM
Symptoms of congenital lymphedema
Unilateral or bilatera leg edema
Swelling of genitalia, face
Lymphedema Praecox frequency of all primary lymphedema
94%
most common form
Meige’s disease
specific familial form of lymphedema praecox
Gender epidemiology of lymphedema praecox
10:1 more female
Clinical presentation of lymphedema praecox
unilateral limited to foot and calf in most patients
Lymphedema tarda frequency of all primary lymphedema
10%
after age 35
Lymphedema classification by morphology
Aplasia: no collecting vessel
Hypoplasia: less number of vessels
Numerical hyperplasia: increase number of vessels only
Hyperplasia: increase number but also tortuous and dilated - megalymphatic and lymphagiectasia
Hyperplasia patterns
more in male
less common than aplasia/hypoplasia
worse prognosis
can also have angioma and chylous reflux
usually unilateral
Ways to classify primary lymphedema
1) time of onset
2) morphology of lymphatic
3) anatomical location of defect
4) clinical setting
Primary lymphedema by anatomy
Distal obstruction (1/3) = agenesis/hypoplasia/obstruction of distal lymphatic with normal proximal vessels
- bilateral and mild swelling
- more in female
- extent of disease usually maxed in first year but can still grow in size
Proximal obstruction (1/2): obstruction of proximal lymphatic/nodes only
- intranodal fibrosis
- unilateral, severe and worsens with time
- more in females if unilateral
- more in male if bilateral hyperplasia
First description of inheritable lymphedema
Milroy 1892 Milroy disease (when inheritable)
Diseases associated with heritable lymphedema
1) Lymphedema-cholestasis (Aagenaes’ syndrome) - 15q realted to VEGFR3
2) lymphedema distichiasis - supplement row of eyelashes from meibomian glands - FOXC2 mutation
3) hypotrichosis lymphedema telangiectasia - SOX18 mutation
Most common cause of secondary lymphedema
Breast cancer 6-30%
Most common cause of secondary lymphedema in 3rd world countries
Filariasis
Filariasis define
1) parasite Wuchereria bancrofti (90%), Brugia malayi, Brugia timori
2) transmitted by mosquitoes
3) perilymphatic inflammation and fibrosis, sclerosis of lymph nodes by adult warms
4) worm products cause reactive hyperplasia and dilation of lymphatic collecting channel
Diagnosis of filariasis
1) eosinophilia
2) microfilariae in peripheral nocturnal blood, urine, lymph
Outcome of filariasis
Filarial lymphedema –> incapacitating elephantiasis
difficult to treat
Other causes of secondary lymphedema
1) trauma - burns, wounds
2) pregnancy
3) infection
4) contact dermatitis
5) RA
Clinical staging from the Working Group of the 10th International Congress of Lymphology
Latent phase: fluid and fibrosis, no apparent edema
Grade I: pitting edema reduced by elevation, no clinical fibrosis
Grade II: non-pitting edema, no improve with elevation, moderate-severe fibrosis
Grade III: irreversible fibrosis, sclerosis, lymphostatic elephantiasis
Mesenteric lymphangiectasia symptoms
Diarrhea
Weight loss
Intermittent drainage of milky fluid from skin vesicles is
reflux of chyle
Signs and symptoms of lymphedema
1) pitting edema
2) square toes
3) positive Stemmer’s sign
4) buffalo hump
5) red skin warm (early) skin
6) thick skin with hyperkeratosis, lichenification, peau d’orange = pigskin (late)
7) recurrent eczematous dermatitis and excoriation
8) verrucae +/- lymphorrhea and chylorrhea
9) yellow nails, clubbing, lack of nail growth
10) aching and heaviness of limb (not intense pain unless infected)
Stemmer’s sign
positive = inability to pinch base of 2nd toe because of inelasticity
Yellow nail syndrome
1) yellow nails from lymphedema
2) pleural effusion
Infection rate in primary lymphedema
31%
Reasons why lymphedema more prone to infection
1) malnutrition
2) impaired local immune response
3) systemic immunodeficiency
4) ample substrate for bacterial growth
5) infection further exacerbates lymphatic drainage
Lymphangiosarcoma
1) multicentric lesions
2) blue nodules
3) sclerotic plaques
4) bullous change
Cancers that can arise from lymphedema
1) lymphangiosarcoma
2) kaposi’s sarcoma
3) SqCC
4) malignant lymphoma
5) melanoma
Lymphocintigraphy key points
1) radiolabelled macromolecular tracer
2) inject subdermal within interdigit webspace
3) gamma camera to trace
Size of particles that get absorbed into lymphatics
larger in the 10 nm range like antimony trisulfide Sb2S3
Different size travel at different time
Sb2S3 - 30-60 min
rhenium - 30-60 min
Tc99m albumin - 10 min
Parameters of lymphoscintigraphy
1) transport kinetics, speed
2) distribution pattern
3) lymph node appearance time
4) lymph node visualizability
5) lymph vessel visualizability
6) abnormal tracer accumulation
Limitation of lymphoscintigraphy
cannot visualize any detail in the foot (injection site)
cannot distinguish between primary vs secondary lymphedema
Signs of lymphedema on lymphoscintigraphy
1) dermal backflow
2) absent/delay transport
3) crossover filling with retrograde backflow
4) delay or absent visualization of lymph node
Signs of lymphangiectasia on lymphoscintigraphy
1) mild or no delay in lymph transport
2) reflux to affected lymphedematous leg can be seen due to valve icnompetence
CT and MRI differentiation of lymphedema from venous edema and lipedema
Lymphedema: confiend to epifascial space of skin and subcutaneous tissue
Venous edema: also affect subfascial muscles
Lipedema: fat accumulation no fluid
help rule out obstructive mass
Direct contrast lymphangiography
1) identify subcu lymphatic with subcu methylene blue injection
2) Direct injection of iodine-based, lipid-soluble agent into subcu lymphatics once identified
3) limited to use before reconstructive surgery
Lipedema
1) Lipodystrophy
2) symmetrical enlargement of lower extremities
3) causes venous insufficiency
4) spares feet
5) cause secondarily cause lymphedema
6) usually morbidly obese
7) normal lymphoscintigraphy and lymphangiography in most cases
Workup for lymphedema
1) systemic work up to rule out other causes of edema (renal, hepatic, hypoproteinemia, eosinophilia)
2) bioimpedance spectroscopy in cancer patients to assess risk of futher lymphedema
3) Venous duplex to rule out venous incompetence
4) Lymphoscintigraphy
Factors that are involved in lymphangiogenesis
VEGF-C and VEGF-D bind VEGFR3 on lymphatic endothelium
