Chapter 168 - Lymphedema introduction

Question 1

Two types of lymphedema and causes

Answer 1

High-input failure = venous edema exceeding maximum transport capacity of lymphatic conduit

low-output failure = compromised lymphatic flow

Question 2

Consequence of lymph stasis

Answer 2

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

Question 3

Clinical classification of lymphedema

Answer 3

Primary lymphedema

Secondary lymphedema

Question 4

Primary lymphedema subclassification

Answer 4

Genetic: familial vs sporadic
Onset: congenital (at birth), praecox (at puberty), tarda (after age 35)

Question 5

Epidemiology of primary lymphedema

Answer 5

1) female 2-10x more often
2) incidence peak age 12-16
3) 1/6000-10000 livebirth

Question 6

Chance of bilateral lymphedema

Answer 6

25%

Question 7

Congenital lymphedema type of transmission

Answer 7

Autosomal dominant

with sporadic penetrance

Question 8

Association of congenital lymphedema with genetic chromosomal abnormalities and syndromes

Answer 8

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

Question 9

Symptoms of congenital lymphedema

Answer 9

Unilateral or bilatera leg edema

Swelling of genitalia, face

Question 10

Lymphedema Praecox frequency of all primary lymphedema

Answer 10

94%

most common form

Question 11

Meige’s disease

Answer 11

specific familial form of lymphedema praecox

Question 12

Gender epidemiology of lymphedema praecox

Answer 12

10:1 more female

Question 13

Clinical presentation of lymphedema praecox

Answer 13

unilateral limited to foot and calf in most patients

Question 14

Lymphedema tarda frequency of all primary lymphedema

Answer 14

10%

after age 35

Question 15

Lymphedema classification by morphology

Answer 15

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

Question 16

Hyperplasia patterns

Answer 16

more in male
less common than aplasia/hypoplasia

worse prognosis

can also have angioma and chylous reflux

usually unilateral

Question 17

Ways to classify primary lymphedema

Answer 17

1) time of onset
2) morphology of lymphatic
3) anatomical location of defect
4) clinical setting

Question 18

Primary lymphedema by anatomy

Answer 18

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

Question 19

First description of inheritable lymphedema

Answer 19

Milroy 1892
Milroy disease (when inheritable)

Question 20

Diseases associated with heritable lymphedema

Answer 20

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

Question 21

Most common cause of secondary lymphedema

Answer 21

Breast cancer 6-30%

Question 22

Most common cause of secondary lymphedema in 3rd world countries

Answer 22

Filariasis

Question 23

Filariasis define

Answer 23

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

Question 24

Diagnosis of filariasis

Answer 24

1) eosinophilia

2) microfilariae in peripheral nocturnal blood, urine, lymph

Question 25

Outcome of filariasis

Answer 25

Filarial lymphedema --> incapacitating elephantiasis difficult to treat

Question 26

Other causes of secondary lymphedema

Answer 26

1) trauma - burns, wounds 2) pregnancy 3) infection 4) contact dermatitis 5) RA

Question 27

Clinical staging from the Working Group of the 10th International Congress of Lymphology

Answer 27

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

Question 28

Mesenteric lymphangiectasia symptoms

Answer 28

Diarrhea | Weight loss

Question 29

Intermittent drainage of milky fluid from skin vesicles is

Answer 29

reflux of chyle

Question 30

Signs and symptoms of lymphedema

Answer 30

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)

Question 31

Stemmer's sign

Answer 31

positive = inability to pinch base of 2nd toe because of inelasticity

Question 32

Yellow nail syndrome

Answer 32

1) yellow nails from lymphedema | 2) pleural effusion

Question 33

Infection rate in primary lymphedema

Answer 33

31%

Question 34

Reasons why lymphedema more prone to infection

Answer 34

1) malnutrition 2) impaired local immune response 3) systemic immunodeficiency 4) ample substrate for bacterial growth 5) infection further exacerbates lymphatic drainage

Question 35

Lymphangiosarcoma

Answer 35

1) multicentric lesions 2) blue nodules 3) sclerotic plaques 4) bullous change

Question 36

Cancers that can arise from lymphedema

Answer 36

1) lymphangiosarcoma 2) kaposi's sarcoma 3) SqCC 4) malignant lymphoma 5) melanoma

Question 37

Lymphocintigraphy key points

Answer 37

1) radiolabelled macromolecular tracer 2) inject subdermal within interdigit webspace 3) gamma camera to trace

Question 38

Size of particles that get absorbed into lymphatics

Answer 38

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

Question 39

Parameters of lymphoscintigraphy

Answer 39

1) transport kinetics, speed 2) distribution pattern 3) lymph node appearance time 4) lymph node visualizability 5) lymph vessel visualizability 6) abnormal tracer accumulation

Question 40

Limitation of lymphoscintigraphy

Answer 40

cannot visualize any detail in the foot (injection site) cannot distinguish between primary vs secondary lymphedema

Question 41

Signs of lymphedema on lymphoscintigraphy

Answer 41

1) dermal backflow 2) absent/delay transport 3) crossover filling with retrograde backflow 4) delay or absent visualization of lymph node

Question 42

Signs of lymphangiectasia on lymphoscintigraphy

Answer 42

1) mild or no delay in lymph transport | 2) reflux to affected lymphedematous leg can be seen due to valve icnompetence

Question 43

CT and MRI differentiation of lymphedema from venous edema and lipedema

Answer 43

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

Question 44

Direct contrast lymphangiography

Answer 44

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

Question 45

Lipedema

Answer 45

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

Question 46

Workup for lymphedema

Answer 46

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

Question 47

Factors that are involved in lymphangiogenesis

Answer 47

VEGF-C and VEGF-D bind VEGFR3 on lymphatic endothelium