Lymphoedema

A disease state in which there is accumulation of interstitial protein rich fluid caused by relative inadequate lymphatic drainage that may either be primary or secondary (acquired).

Pathophysiology
Venous capillary system returns 90% of fluid
Lymph the rest, but also largest macromolecules
--> failure of lymph causes accumulation of interstitial fluid and proteins.
As disease progresses:
- get increasing dilation of lymphatic channels
--> lymph valvular incompetence and reversal of flow.
- lymphatic walls undergo fibrosis
--> fibrinoid thrombi obliterate remaining patent channels.

- interstitial protein stasis causes an inflammatory response
--> macrophages and fibroblasts replace elastic interstitium with thickened congested tissues
Eventually, soft pitting oedema gives way to induration
- hypertrophy of adipose deposits, acanthosis, hyperkeratosis, skin breakdown.

Complications
Infections
Rarely, lymphosarcoma

2 main pathologies:

1) High input failure: eg venous insufficiency where hydrostatic pressures cause interstitial fluid accumulation that is beyond the capacity of the lymphatic system to drain

2) Low-output failure: some form of lymphatic channel dysfunction leads to oedema.

Leads to hyaluronic acid and GAGs in the extracellular space plus cell debris. This then leads to an increase in fibroblasts and macrophages in the extracellular space and hence collagen deposition (fibrosis occurs).

Primary Lymphoedema:
Congenital but with delayed presentation
- Females affected more than males, unilateral more common than bilateral. Associated with aneuploidic disorders such as kleinfelters, downs etc

Subclassified by age of onset:

1) Congenital lymphedema: present at birth or within first year of life

a. Milroy’s disease: an autosomal dominant familial form, mutation in VEGFR-3 gene

b. Nonfamilial, sporadic: more common, males>females

2) Lymphoedema praecox: most common primary lymphedema. Onset after 1 year of age, seen in females, foot and calf oedema

3) Lymphoedema tarda: uncommon, after age 35

Subclassified by morphology:

1) Aplasia: no lymph seen

2) Hypoplasia: few lymph

3) Numerical hyperplasia: many number of lymph channels seen

4) Hyperplasia: large lymphatics with incompetent valves.

Subclassifed by anatomy:

1) distal obstruction

2) proximal pbstruction

Secondary Lymphoedema:

Seen by surgeons.
Cancer: breast cancer axillary dissection and radiotherapy independently cause lymphatic obstruction. Gynae cancer, urological cancer and melanoma surgery, all involving lymph node harvest can lead to lymphoedma

Filariasis: caused by nematodes; Wucheria bancrofti, Brugia malayi, Brugia timori, most common cause in 3^rd world countries: worms cause perilymphatic inflammation, eosinophillia on bloods, microfilaria on nocturnal blood smears: rapidly progresses to elephantiasis: difficult to treat.

Burns, large or circumferential wounds, pregnancy, bacterial and fungal infections, snake and insect bites, contact dermatitis, rheumatoid arthritis.
Trauma, infection and obesity are also important causes.

Staging

Latent Phase: excess fluid in tissue but no oedema seen

Grade 1: Spontaneously reversible: edema pits on pressure but the oedema is reduced by simple limb elevation

Grade 2: Sponteanously irreversible. Non-pitting oedema, moderate to severe fibrosis of the tissue. Does not resolve with elevation.

Grade 3: :Lymphostatic elephantiasis. Irreversible oedema with repeated inflammatory attacks, severe fibrosis, sclerosis of skin and subcutaeneous tissues, lymphostatic elephantiasis

Workup

History:

1)Family History

2) diarrhoea and weight loss: suggests mesenteric lymphangiectasia

3) milky fluid weeping: chylous reflux

4) history of lymph node dissection/ cancer/ irradiation, trauma, infection

5) travel to tropical countries: filiriasis

Workup for other causes of oedema: cardiac, venous, renal, hepatic, compressive / occlusive vascular disease

Examination:

Oedema: frequently extends to the distal aspects of the toes resulting in square toes (Stemmers sign. Dorsum of forefoot is swollen: buffalo hump

Skin changes:

a) early: pink/red skin, warm

b) late: thickened skin

a. hyperkeratosis

b. lichenification

c. peau d’orange

d. eczematous dermatitis:

e. ulceration is rare

f. Verrucae and vessicles

i. Lymphorrhaea

ii. Chylorhaea

c) Yellow Nail syndrome: primary lymphoedema with pleural effusions

Investigations:

1) Lymphoscintagrphy

a. Radiolabelled tracer injected subdermally in interdigital space

b. Transport tracked with gamma camera

c. Can identify lymphatic transport time, lymphatic trunks and anatomy of lymph nodes

d. In lymphoedmea:

i. Dermal back flow

ii. Delayed transport of tracer

iii. Channels obliterated, or ectatic

e. In lymphangiectasia

i. Multiple dilated lymph channels

ii. Reflux from normal to abnormal leg

2) Direct contrast Lymphography:

a. A preoperative test only, methylene blue injected in tissue to identify lymphatics thence cannulation of lymph channels and dye injection.

3) Lymphatic capillaroscopy

4) MRI: lymphoedema is typically confined to the subcutaneous space, muscles are spared. Honeycomb appearance, (in venous oedema there is epifascial and subfascial oedema. Lymph nodes may be seen

5) ultrasound

Majority of patients diagnosed clinically without such investigations

Differential diagnosis:

1) Lipedema: bilateral swelling in obese females (cankles)

a. Sparing of the feet despite large calves and thighs

2) Venous insufficiency (chronic inflammation in the subcutaenous space may destroy lymph channels and thus lead to lymphatic insufficiency.

3) Congenital vascular malformation

4) Arteriovenous fistula

5) Trauma: reflex sympathetic dystrophy

6) Snake or insect bite

7) Infection/ inflammation

8) Haematoma

9) Dependancy

10) Rheumatoid arthritis

11) Post revascularisation oedema

12) Soft tissue tumour

13) Systemic causes:

a. Cardiac/ hepatic/ renal failure

b. Low protein

c. Hyperthyroidism

d. Drugs: antihypertensives, hormones

Potential Comlpications:

Infection: recurrent soft tissue infection

Malnutrition and immunodeficiency: protein losing enteropathy, chylous ascities, chylothorax: loss of proteins and triglycerides, loss of inflammatory cytokines etc

Malignancy: lymphangiosarcoma may develop rarely as a result of lymphoedema

Therapy

Challenging.

Principles

Reduction of proteinaceous interstitial fluid, stemming cycles of oedema, inflammation and fibrosis
Skin care and compression

Non-operative management:

1) Skin hygiene

2) Cotton clothing

3) Avoid trauma, treat any cuts with topical antibiotics

4) Apply topical antifungals regularly

5) Treat infections with systemic antibiotics even if minimal lymphoedema

6) Limb elevation

7) Exercise

8) Weight management, low sodium

9) Avoid pressure to limb

10) Pt education

11) ? diuretics
--> historic; may actually worsen interstitial protein accumulation and fibrosis.

12) Limb elevation

13) Low stretch bandaging: increase lymph flow in walking

14) Stockings: go for high 40-50 Grade 4 Jobst, long enough to cover oedema

--> important to compress the fluid; reduce oedema volume 30-45%;

15) Massage

16) Pneumatic pump

Surgical Management
Reserved for moderate to severe cases and indications not well clarified
Historically, the radical Charles procedure stripped away to fascia and grafted the excised skin
Modified Sistrunk procedure strips away subcut tissue in stages; safe reliable and predictable
- debulk while leaving sufficient dermal flaps to bury with closure; closed over drains and repeated in 12w
Liposuction is another option; safe, quick, immediate decrease in volume
Physiologic Procedures:
- aim to restore normal physiology by improving lymph drainage
- microvascular lymphatic shunts; established microvascular connections to lymph channels