Lymphoedema

Section: Breast Curriculum: Curriculum, page 16

Definition

• Accumulation of protein-rich interstitial fluid secondary to the lymphatic load exceeding the transport capacity of the lymphatic flow
• Low output failure of lymphovascular system

Classification

International society of lymphology staging

• Stage 0 - subclinical or latent lymphoedema. Patients are asymptomatic.
• Stage I - early accumulation of fluid. Pitting may occur.
• Stage II - associated with fatty hypertrophy and skin thickening.
• Stage III - pitting is absent. Swelling is significant. Skin becomes thick, leathery, with warty overgrowths.

Aetiology

• Primary - inherited or genetic (F>M and LL)
  • Familial lymphoedema
  • Congenital primary lymphoedema → lymphatic hypoplasia
  • Idiopathic lymphoedema → mainly LL
• Secondary
  • Iatrogenic (post-surgical)
    • SNB/AND
    • Lymphadenectomy
    • Recurrent varicose V surgery
  • Cancer
    • Tumour extrinsic compression
    • Lymphangiosarcoma
    • Surgery, RTX and meds
  • Infection
    • Filariasis most common - nematode infection (Wuchereria banicrofti)
    • Recurrent cellulitis
  • RTX
  • Trauma

Primary

• Rare 1:10,000
• Familial Lymphoedema
  • Usually bilateral & below knee
  • AD inheritance (but variable expression)
  • Associated with distichia (abnormal lash growth), extradural cysts, vertebral anomalies, CVS malformations, yellow nails & sensorineural hearing loss
• Based on Age of Onset
  • < 2 = Congenital Milroy’s
    • Incidence 1:33000; M > F
    • Lymphatic hypoplasia / aplasia
    • Presents within 1 year of birth
    • Usually bilateral
  • 2-35 = Lymphoedema Praecox
    • Praecox = Very early
    • Most common: 80%
  • Meige’s Disease
    • Age > 35 = Lymphoedema Tarda
• Idiopathic
  • Incidence 1:6000, F > M (3:1)
  • Lower limb usually affected
  • Distal obliterative lymphoedema (90%)
    • Affects girls at puberty
      • Due to ↓ / absent lymphatics
  • Proximal obliterative lymphoedema
    • M>F (2:1); 50% are bilaterally
    • ↓ed / fibrotic inguinal / pelvic LNs
  • Massive, localized lymphedema of thigh
  • Predisposing factors: Obesity, Hypothyroidism, trauma/surgery
  • Mega-lymphatics – Absence of lymphatic valves → Reflux ± Fistulation into pleural / peritoneal / uterine cavity

Secondary

• Most Common
• Extrinsic damage to lymphatics
  • Malignant obstruction
    • Peu d’orange
    • Kaposi’s Sarcoma
  • Surgery
    • Arterial/venous surgery
    • Groin or axillary dissection
  • Chronic Venous Insufficiency
    • Phlebolymphoedema: Lymphatic dysfunction in advanced chronic venous insufficiency
  • Trauma
  • Radiotherapy
  • Infection
    • World-wide most common - Filarial infection: Wuchereria bancrofti & Brugia
    • Parasite Nematode – Round worm
      • Elephantiasis
      • Rx: Albendazole
    • Others: TB, Fungi
  • Rheumatoid Arthritis/ Psoriatric Arthritis – mechanism uncertain

Post Surgical Lymphoedema

• LN surgery in Groin → up to 50% risk
• Most common in developed countries – Breast Cancer treatment
• Normally pressure in lymphatics negative or 0 mmH20, but after axillary dissection intra-lymphatic pressure becomes positive, and lymphatic flow can be 10 x slower
• Mastectomy itself leads to fibrosis in axilla & there may be increased arterial flow due to loss of sympathetic vascular tone
• Predisposing factors after breast surgery
  • Radiotherapy
  • Obesity
  • Age
  • Operative site (SNB or limiting dissection to level 1 and 2 better)
  • Incision type (transverse better than oblique)
  • Infection
• Incidence
  • Post mastectomy – acute arm oedema 40% - most resolve
    • Chronic lymphedema 3-20%
    • Radiotherapy + AD – 52%
    • Infection affects risk
  • Exacerbating Factors
    • Radical AD
    • Poor haemostasis
    • Closure under tension
    • Large potential space
    • Infection – prophylaxis reduces rate

Risk Factors

• Hereditary syndromes
• Maligancy and its treatments
• Increasing age
• Obesity
• Autoimmune disease
• Inflammatory arthritis
• Specific risk factors for lymphoedema in those with breast cancer and RTX tx
  • AND
  • Higher grade, more advanced and large tumours with nodal involvement and postoperative local complications

Pathophysiology

• Normally lymphatic drainage is closely associated with vessel properties and Starling’s law
  • Low pressure system with unidirectional valves and SM, flow aided by SM contraction
  • Lower body, GIT and left upper body drains to thoracic duct and into jxn between left IJV and left subclavian
  • Right upper body in right lymphatic duct and into same on right side
• Steps
  • 1. Lymphatic Dysfunction/Disruption
  • 2. Lymph Statsis and Accumulation
    • Leads to increase in protein-rich interstitial fluid, which exerts an osmotic effect and attracts additional water.
  • 3. Chronic inflammation
    • Protein rich fluid causes inflammation - Inflammatory cascade → cytokines etc
    • Lymphangiogenesis
      • Attempts to compensate for impaired drainage result in new lymphatic vessel formation.
      • These vessels are often leaky and dysfunctional, exacerbating fluid accumulation.
  • 4. Tissue Remodeling and fibrosis
    • Chronic inflammation leads to fibroblast activation, resulting in excessive collagen deposition and tissue fibrosis.
    • This creates a cycle of further lymphatic obstruction and impaired drainage.
    • Adipose Deposition
      • In long-standing lymphedema, fat deposition in the affected tissues occurs.
      • Adipogenesis is driven by inflammatory mediators and local tissue hypoxia.

Presentation

• Slowly progressing sx
• Swelling, skin change and non-pitting oedema (early it is pitting)
• Discomfort of limbs at rest and with movement
• Restricted ROM
• Dermal thickening with less pitting and cutaneous fibrosis, adipose deposition
• Stemmer sign - can’t lift a thick skin fold off 2nd digit (toe or finger) base = lymphoedema

Investigations

• Arm measurements - circumference and volume - fixed points
  • From fixed anatomic landmarks
  • Measure at MCPJ if involved, wrist, 10cm distal and prox to olecranon
  • Leg - MTPJ, 2cm sup to medial malleolus, 10cm distal and prox to inf and sup pole of patella

  • 2cm diff between affected and non affected side = clinically sig

• Volume measurement
  • Water displacement or optoelectronic volumetry (infrared)
  • Limb volume calculation with truncated cone formula
  • 4cm increments circumference measured of limb (from wrist or ankle)
  • Converted to volume using truncated cone formula
• Water displacement
  • Detects change in volume <1%
  • Negatives - large, expensive, prone to leak
• Optoeletronic voluntary
  • Better than displacement for UL measurement
  • Expensive
  • Limb volume calculation
  • More measurements so more informative but likely impacted by obesity
  • Relies on formula to represent shape of leg
• Imaging
  • Duplex USS - R/O venous insufficiency
  • CT/MRI - R/O obstruction lesions e.g. thoracic outlet obstruction
• Lymphoscintigraphy
  • Can be used to look at lymphatic flow - can help differentiate between other causes of swelling.

DDX

• Chronic venous insufficiency - not varicose
• DVT
  • Post thrombotic syndrome - after DVT
• Limb hypertrophy
• Lipedema - abnormal fat deposition with oedema
• Myxedema - hypothyroid and non pitting
• Tumour

Management

• Principles
  • Treating underlying cause
  • Avoidance and early treatment of infection
  • Promotion of lymph flow to prevent chronic changes
• Interventions
  • CONSERVATIVE MULTIMODAL THERAPY
    • Massage
      • PT/manual lymph drainage (lymphatic massage)
    • Elevation
    • Exercise - gradual and regular
    • Graduated compression (50-60% reduction)
      • Correctly measured and fitted
      • Maintenance - at least class 1
      • Wear while awake
    • Intermittent pneumatic compression
    • Avoid trauma
• Surgical
  • Indications
    • Failed non-op and
    • Significant disease affecting life - pain, deformity
    • Recurrent cellulitis
    • Lymph leakage into body cavity or externally
  • Options
    • Lymphatic bypass - lymph-lymph, lymph-vein, lymph-venule
      • Variable response
    • Reduction
      • Ablation, removal of fibrofatty tissue
      • Excision
      • Liposuction

Prevention

• Avoid lymphatic surgery - AND….
• RTX targeted if at all needed
• PT/exercise
• Good skin hygiene/limb care
• No BP checks or procedures on that arm
• Graduated compression stockings

Complications

• Cellulitis
• Psychological
• Lymphangiosarcoma

Prognosis

• Increased risk of lymphangiosarcoma with chronic lymphoedema
• Early PT/lymphoedema nurse referral