Skip to content
Download PDF

Chronic Venous Disease and Lymphedema

Chapter 293 | Part 6: Disorders of the Cardiovascular System · Part 6 – Cardiovascular Disorders · Chapter 293

Key Clinical Points

  1. Varicose veins prevalence: ~15% in men, 30% in women; increases with age (2% in those <50 years → 10% in those 70 years).
  2. Chronic venous insufficiency (CVI) prevalence: ~7.5% in men, 5% in women.
  3. CEAP Classification: Standardized system for Clinical (C), Etiologic (E), Anatomic (A), and Pathophysiologic (P) assessment of venous disease.
  4. Frostbite rewarming: Must be performed in a water bath at 40°–44°C (104°–111°F); massage, ice water, and extreme heat are strictly contraindicated.
  5. Lymphedema Staging: Stage 0 (latent), Stage I (pitting), Stage II (nonpitting/mixed), Stage III (woody/indurated).
  6. Endovenous thermal ablation occlusion rates: >90% at both 1 and 5 years.
  7. Sclerotherapy occlusion rates: 81% at 1 year, 74% at 5 years.
  8. Stemmer's sign: Inability to tent the skin at the base of the toes; a key diagnostic finding for lymphedema.
  9. Lymphedema MRI findings: Honeycomb pattern in the epifascial compartment.
  10. Primary lymphedema genetic causes: Milroy's disease (VEGFR3), Meige's disease, Lymphedema-distichiasis (FOXC2).

DEFINITION & OVERVIEW

• Erythromelalgia: Definition: A disorder characterized by burning pain and erythema of the extremities. ◦ Clinical Features: Feet involved more frequently than hands; males affected more frequently than females. May occur at any age, most common in middle age. ◦ Types: Primary (erythermalgia) or secondary. ◦ Genetics: Mutations in the SCN9A gene (encoding Nav1.7 voltage-gated sodium channel) are associated with inherited forms. ◦ Secondary Causes: Myeloproliferative disorders (polycythemia vera, essential thrombocytosis); Drugs (calcium channel blockers, bromocriptine, pergolide); Neuropathies; Connective tissue diseases (SLE); Paraneoplastic syndromes. ◦ Symptoms: Burning in extremities precipitated by warm environment and aggravated by dependent position. Relieved by cool air/water or elevation. ◦ Differentiation: Distinguished from ischemia by the presence of peripheral pulses. ◦ Management: No specific treatment; aspirin may provide relief in secondary cases. Options include topical anesthetics (lidocaine), combination of amitriptyline and ketamine, or topical midodrine.

• Frostbite: Definition: Tissue damage resulting from severe environmental cold exposure or direct contact with a very cold object. ◦ Mechanism: Result of both freezing and vasoconstriction. ◦ Severity: ◦ Superficial: Involves skin and subcutaneous tissue; presents as pain/paresthesia, white/waxy appearance. After rewarming: cyanosis, erythema, wheal-and-flare, edema, superficial blisters. ◦ Deep: Involves muscle, nerves, and deeper blood vessels; leads to edema, vesicles/bullae, tissue necrosis, gangrene. ◦ Management: ◦ Initial Step: Move to an environment where re-exposure to freezing is impossible. ◦ Rewarming: Immersion in water bath at 40°–44°C (104°–111°F). ◦ Contraindications: Massage, ice water, and extreme heat. ◦ Care: Clean with soap/antiseptic; apply sterile dressings. Analgesics often required during rewarming; antibiotics if infection is present.

• Chronic Venous Disease (CVD): Definition: Spectrum ranging from telangiectasias and reticular veins to varicose veins, and chronic venous insufficiency with edema, skin changes, and ulceration.

• Lymphedema: Definition: A chronic condition caused by impaired transport of lymph, characterized by swelling of one or more limbs (occasionally trunk/genitalia). ◦ Pathophysiology: Imbalance between lymph production and absorption → accumulation of proteins in interstitial tissues → increased osmotic load → water accumulation. ◦ Chronic Response: Inflammation/immune response → infiltration of mononuclear cells, fibroblasts, and adipocytes → adipose and collagen deposition in skin/subcutaneous tissue.

EPIDEMIOLOGY

• Varicose Veins: ◦ Prevalence (US): ~15% in men; 30% in women. ◦ Age Correlation: 2% in those <50 years → 10% in those 70 years of age.

• Chronic Venous Insufficiency (CVI) with Edema: ◦ Prevalence (US): ~7.5% in men; 5% in women. ◦ Age Correlation: 2% in those <50 years → 10% in those 70 years of age.

• Venous Ulcers: Approximately 20% of patients with CVI develop venous ulcers.

• Primary Lymphedema: ◦ Prevalence: ~1.15 per 100,000 persons <20 years of age. ◦ Gender: Females affected more frequently than males.

ETIOLOGY & PATHOPHYSIOLOGY

• Venous Anatomy: ◦ Superficial System: ◦ Great saphenous vein: Longest in body; medial side of foot → anterior to medial malleolus → medial calf/thigh → common femoral vein. ◦ Small saphenous vein: Dorsolateral foot → posterior to lateral malleolus → popliteal vein. ◦ Deep System: ◦ Pairs (e.g., posterior tibial, anterior tibial, peroneal) → Popliteal → Femoral → External iliac → Inferior vena cava. ◦ Perforating Veins: Connect superficial and deep systems at multiple locations.

• Pathophysiology of Chronic Venous Disease: ◦ Var1: Varicose veins (dilated, bulging, tortuous; ≥ 3 mm diameter). ◦ Var2: Reticular veins (dilated intradermal; 1–3 mm; do not protrude from skin surface). ◦ Var3: Telangiectasias (small, dilated; <1 mm; near skin surface). ◦ Primary Varicose Veins: Result from defective structure/function of saphenous valves; ~50% have family history. ◦ Secondary Varicose Veins: Result from venous hypertension (deep-venous insufficiency, incompetent perforators, or arteriovenous fistulas).

• Chronic Venous Insufficiency (CVI): ◦ Mechanism: Incompetent veins → venous hypertension → extravasation of fluid and blood elements into tissue. ◦ Primary: Intrinsic structural/functional abnormality in vein wall or valves. ◦ Secondary: Obstruction/incompetence from previous DVT; May-Thurner syndrome (left iliac vein compression); tumor compression; AV fistulas; congenital malformations (Klippel-Trénaunay, Parkes-Weber).

• Lymphedema Etiology: ◦ Primary: ◦ Sporadic (no identified cause). ◦ Genetic Disorders: Milroy's disease (VEGFR3, VEGF-C); Meige's disease; Lymphedema-distichiasis (FOXC2); Cholestasis-lymphedema (LSC1); Hennekam's lymphangiectasia-lymphedema (CCBE1); Emberger's syndrome (GATA2); Microcephaly-lymphedema (KIF11); Hypotrichosis-lymphedema-telangiectasia (SOX18). ◦ Chromosomal: Turner, Klinefelter, Trisomies 13, 18, or 21. ◦ Syndromic: Noonan's, Klippel-Trénaunay, Parkes-Weber, Yellow nail, Intestinal lymphangiectasia, Lymphangiomyomatosis, Neurofibromatosis type 1. ◦ Secondary: ◦ Infection: Bacterial (S. pyogenes, S. aureus), Lymphogranuloma venereum (C. trachomatis), Filariasis (W. bancrofti, B. malayi, B. timori), Tuberculosis. ◦ Neoplastic: Lymphoma, Prostate cancer. ◦ Iatrogenic: Surgery/radiation of axillary/inguinal nodes; iatrogenic division during bypass or varicose surgery. ◦ Miscellaneous: Phlebolymphedema (CVI), Contact dermatitis, Podoconiosis, Rheumatoid arthritis, Pregnancy, Factitious.

CLINICAL FEATURES

• Varicose Veins & CVI: ◦ Symptoms: Dull ache, throbbing, heaviness, pressure; Cramping, burning, pruritus, swelling. ◦ Clinical Findings: Edema (usually pitting), stasis dermatitis, skin ulceration near ankle. ◦ Dermatologic Features: ◦ Lipodermatosclerosis: Induration + hemos1eridin deposition + inflammation. ◦ Atrophie blanche: White scar tissue with telangiectasias and hyperpigmented border. ◦ Corona phlebectatica: Fan-shaped intradermal veins near ankle/foot.

• Lymphedema Features: ◦ Symptoms: Generally painless; chronic dull, heavy sensation. ◦ Progression: Foot → leg → loss of normal contour; 'squaring' of the toes. ◦ Physical Signs: ◦ Early: Soft, pitting edema. ◦ Late: Nonpitting, woody texture (fibrosis/adipose deposition). ◦ Stemmer's sign: Inability to tent skin at the base of the toes. ◦ Peau d'orange: Dimpling of skin resembling orange peel.

• Lymphedema Staging: Reference Table 293-3 1. Stage 0 (Ia): Latent/subclinical; no evident swelling despite impaired transport. 2. Stage I: Early accumulation; high protein content; subsides with limb elevation; pitting may occur. 3. Stage II: Limb elevation rarely reduces tissue swelling; pitting is manifest. Late stage → may not pit due. to fat/fibrosis. 4. Stage III: Lymphostatic elephantiasis; no pitting; acanthosis, fat deposition, and warty overgrowths.

DIFFERENTIAL DIAGNOSIS

• CVI vs. Acute DVT: ◦ Distinction: Duration of leg edema. • Lymphedema vs. CVI: ◦ Note: Can occur together (phlebolymphedema) if venous insufficiency impairs lymphatic function. • Bilateral Leg Swelling: ◦ Congestive heart failure; Hypoalbuminemia (Nephrotic syndrome); Severe hepatic disease; Myxedema (Hypothyroidism or Graves' pretibial myxedema); Drugs (Dihydropyridine CCBs, Thiazolidinediones). • Unilateral Leg Swelling: ◦ Ruptured muscles; Hematomas; Popliteal cysts; Cellulitis; Vasculitis; Skin cancer; Neuropathies (Diabetes); Hydroxyurea complication.

DIAGNOSTIC APPROACH

  1. Venous Duplex Ultrasonography:
  2. Primary diagnostic test using B-mode imaging and spectral Doppler.
  3. Purpose: Detect obstruction and reflux in superficial/deep veins.
  4. Obstruction Diagnosis:
  5. Criteria 1: Absence of flow.
  6. Criteria 2: Presence of echogenic thrombus.
  7. Criteria 3: Failure to collapse under compression → indicates intraluminal thrombus.
  8. Venous Reflux Detection:
  9. Method: Prolonged reversal of flow during Valsalva maneuver (especially common femoral).
  10. Bedside Maneuvers:
  11. Brodie-Trendelenburg test:
  12. Procedure: Supine → elevate leg → place tourniquet on thigh → stand.
  13. Result: Filling of veins within 30s → indicates deep-venous insufficiency and incompetent perforators.
  14. Perthes test:
  15. Procedure: Stand with tourniquet on midtherm (veins filled) → walk for 5 min.
  16. Result: Superficial veins distend further → suggests deep-venous obstruction.

MANAGEMENT & TREATMENT

  1. Frostbite Management:
  2. Step 1: Move to environment where re-exposure to freezing is impossible.
  3. Step 2: Immerse affected part in water bath at 40°–44°C (104°–111°F).
  4. Step 3: Clean with soap/antiseptic; apply sterile dressings.
  5. Note: Analgesics often required during rewarming; antibiotics if infection present.
  6. Contraindications: Massage, ice water, extreme heat.
  7. Erythromelalgia Treatment:
  8. No specific treatment.
  9. Options: Aspirin (if secondary), topical anesthetics (lidocaine), amitriptyline + ketamine, or topical midodrine.
  10. Lymphedema Management:
  11. Clinical focus on managing progression from pitting to nonpitting edema and skin changes.

COMPLICATIONS & PROGNOSIS

• Venous Ulcers: ◦ Risk: Approximately 20% of patients with CVI develop these. • Frostbite Sequelae: ◦ After recovery, affected extremity may exhibit increased sensitivity to cold.

KEY PEARLS & CLINICAL TRAPS

• Stemmer's Sign: Pathognomonic for lymphedema; inability to tent skin at the base of toes. • Frostbite Temperature: Must be 40°–44°C (104°–111°F) for rewarming. • CEAP Classification: - C0: No signs; C1: Telangiectasias/reticular; C2: Varicose; C3: Edema; C4: Skin changes (4a: Pigmentation/eczema, 4b: Lipodermatosclerosis/atrophie blanche, 4c: Corona phlebectatica); C5: Healed ulcer; C6: Active ulcer. - E: Primary; Secondary (Si=intravenous, Se=extravenous); Congenital; None identified. - A: Superficial; Perforator; Deep; Not identified. - P: Reflux; Obstruction; Both; Not identified. • Lymphedema Stages: - Stage I: Pitting; Stage II: Nonpitting/mixed; Stage III: Elephantiasis/woody appearance. • Intervention Success: - Endovenous thermal ablation: >90% occlusion at 1 and 5 years. - Sclerotherapy: 81% at 1 year, 74% at 5 years.

Reference Tables

TABLE 293-1 CEAP (Clinical, Etiologic, Anatomic, Pathophysiologic) Classification Clinical Classification C No visible…

Harrison's 22e, p.2181

  • Clinical Classification
  • C No visible or palpable signs of venous disease
    0
  • C Telangiectasias or reticular veins
    1
  • C Varicose veins
    2
  • C Recurrent varicose veins
    2r
  • C Edema
    3
  • C Changes in skin and subcutaneous secondary to CVD
    4
  • C Pigmentation or eczema
    4a
  • C Lipodermatosclerosis or atrophie blanche
    4b
  • C Corona phlebectatica
    4c
  • C Healed venous ulcer
    5
  • C Active venous ulcer
    6
  • C Recurrent active venous ulcer
    6r
  • Etiologic Classification
  • E Primary
    p
  • E Secondary
    s
  • E Secondary – intravenous
    si
  • E Secondary – extravenous
    se
  • E Congenital
    c
  • E No cause identified
    n
  • Anatomic Classification
  • A Superficial
    s
  • A Perforator
    p
  • A Deep
    d
  • A No venous anatomic location identified
    n
  • Pathophysiologic Classification
  • P Reflux
    r
  • P Obstruction
    o
  • P Reflux and obstruction
    r,o
  • P No pathophysiology identified
    n

TABLE 293-2 Causes of Lymphedema Primary Sporadic (no identified cause) Genetic disorders

Harrison's 22e, p.2183

  • Primary
  • Sporadic (no identified cause)
    Genetic disorders
  • Milroy’s disease (VEGFR3, VEGF-C)
    Meige’s disease (gene mutation not established)
    Lymphedema-distichiasis syndrome (FOXC2)
    Cholestasis-lymphedema (LSC1)
    Hennekam’s lymphangiectasia-lymphedema syndrome (LCCBE1)
    Emberger’s syndrome-lymphedema and predisposition to AML (GATA2)
    Microcephaly-lymphedema syndrome (KIF11)
    Hypotrichosis-lymphedema-telangiectasia (SOX18)
  • Chromosomal aneuploidies
    Turner’s syndrome
  • Klinefelter’s syndrome
  • Trisomy 13, 18, or 21
  • Other disorders associated with primary lymphedema
  • Noonan’s syndrome
  • Klippel-Trénaunay syndrome
  • Parkes-Weber syndrome
  • Yellow nail syndrome
  • Intestinal lymphangiectasia syndrome
  • Lymphangiomyomatosis
  • Neurofibromatosis type 1
  • Secondary
  • Infection
  • Bacterial lymphangitis (Streptococcus pyogenes, Staphylococcus aureus)
  • Lymphogranuloma venereum (Chlamydia trachomatis)
  • Filariasis (Wucheria bancrofti, Brugia malayi, B. timori)
  • Tuberculosis
  • Neoplastic infiltration of lymph nodes
  • Lymphoma
  • Prostate
  • Others
  • Surgery or irradiation of axillary or inguinal lymph nodes for treatment of
    cancer Iatrogenic
  • L ymphatic division (during peripheral bypass surgery, varicose vein surgery,
    or harvesting of saphenous veins)
  • Miscellaneous
  • Chronic venous insufficiency
  • Contact dermatitis
  • Podoconiosis
  • Rheumatoid arthritis
  • Pregnancy
  • Factitious

TABLE 293-3 Stages of Lymphedema Stage 0 (or Ia) A latent or subclinical condition where swelling is not evident…

Harrison's 22e, p.2184

  • Stage 0 (or Ia)
  • A latent or subclinical condition where swelling is not evident despite impaired
    lymph transport. It may exist for months or years before overt edema occurs.
  • Stage I
  • Early accumulation of fluid relatively high in protein content that subsides with
    limb elevation. Pitting may occur. An increase in proliferating cells may also be
    seen.
  • Stage II
  • Limb elevation alone rarely reduces tissue swelling, and pitting is manifest. Late
    in stage II, the limb may or may not pit as excess fat and fibrosis supervene.
  • Stage III
  • Lymphostatic elephantiasis where pitting can be absent and trophic skin
    changes such as acanthosis, further deposition of fat and fibrosis, and warty
    overgrowths have developed.