Cryotherapy

Aka: Cryotherapy, Liquid Nitrogen, LN2, Cutaneous Cryosurgery, Cryosurgery

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II. Definitions

  1. Cryotherapy (Cryosurgery)
    1. Directed tissue destruction via the application of freezing Temperatures

III. Indications: Cryotherapy (Cryosurgery)

  1. See Margin sizes below under technique
  2. Short freeze times (5 seconds after freeze ball forms)
    1. Actinic Keratoses
    2. Skin Tags
    3. Lentigines
  3. Moderate freeze times (10 seconds after freeze ball)
    1. Common Wart
    2. Cherry Angioma (consider cryoprobe)
    3. Cutaneous horn
    4. Oral Mucocele (consider cryoprobe)
    5. Pyogenic Granuloma
    6. Sebaceous Hyperplasia (consider cryoprobe)
  4. Longer freeze times (20 seconds after freeze ball)
    1. Hypertrophic Scar or Keloid
    2. Seborrheic Keratoses
    3. Dermatofibroma
    4. Digital Mucous Cysts
    5. Keratocanthoma
    6. Bowen Disease
  5. Very long freeze times (30 seconds after freeze ball with 5 mm margin)
    1. Lentigo maligna
    2. Basal Cell Carcinoma
    3. Squamous Cell Carcinoma

IV. Contraindications: Cryotherapy (Cryosurgery)

  1. Immunosuppression
  2. Agammaglobulinemia
  3. Cryoglobulinemia
  4. Multiple Myeloma and idiopathic blood dyscrasias
  5. Pyoderma Gangrenosum
  6. Cold Urticaria
  7. Bullous Conditions
  8. Exercise caution
    1. Patients with dark skin
    2. Lesions on bony prominences
    3. Anticoagulant Use
  9. Avoid use in distal extremities in high-risk patients
    1. Raynaud's Syndrome
    2. Acrosclerosis or Scleroderma
    3. Peripheral Neuropathy
      1. Diabetes Mellitus
      2. Leprosy
    4. Peripheral Vascular Disease
  10. Cancerous skin lesions not amenable to Cryotherapy
    1. Melanoma (excision required in all cases)
    2. Squamous Cell Carcinoma that is not well differentiated
    3. Basal Cell Carcinoma that is not nodular or superficial type
      1. Morpheaform
      2. Sclerosing
      3. Infiltrating
      4. Micronodular
      5. Metatypical
    4. High risk skin sites
      1. Nose or nasolabial folds
      2. Ear
      3. Chin
      4. Temple
    5. Lesion deeper than 3mm or of diameter >2 cm
    6. Recurrent lesions
    7. Ulcerated lesions
    8. Lesions fixed to deeper structures
    9. Poorly demarcated lesion or lesions fixed to underlying tissue

V. Mechanism

  1. Liquid Nitrogen boils at -196 C (-320 F)
  2. CryoSpray and CryoProbe: Skin Temperature down to -25 to -50 C (-13 to -58 F) at 30 secs
    1. Benign lesions destroyed at -20 to -30 C (-4 to -22 F)
    2. Malignant lesions destroyed at -40 to -50 C (-40 to -58 F)
  3. Cotton or Synthetic Applicator: Skin Temperature does not reach the same degree of freeze as CryoSpray or CryoProbe
    1. Temperature reached is not sufficient for malignant lesions
    2. Temperature is sufficient for benign lesions
  4. Skin lesion destruction
    1. Results from intracellular ice formation, osmolarity changes and localized vascular stasis
    2. Inflammation occurs within 24 hours of Cryotherapy
    3. Tissue injury is greater with technique
      1. Rapid freezing and slowly thawing
      2. Repeat freeze-thaw cycles

VI. Preparation: Storage of Liquid Nitrogen

  1. Store Liquid Nitrogen in proper container (e.g. Dewar)
    1. Prevents serious explosion
    2. Container should allow some leakage/evaporation
    3. Storage vessel should be metal lined (Not glass)
  2. Do NOT pour Liquid Nitrogen back into Dewar after use
    1. May contaminate main supply
    2. HPV, HSV, and Hepatitis viable for years at -196 C
  3. Static Holding time in a standard Dewar
    1. Volume 5L: 6 days
    2. Volume 10L: 45 days
    3. Volume 25L: 110 days
    4. Volume 35L: 110 days
    5. Volume 45L: 125 days

VII. Adverse Effects

  1. Initial
    1. Blistering
    2. Bleeding
    3. Pain
  2. Later
    1. Hypopigmentation (Melanocytes are very cold sensitive)
    2. Hyperpigmentation (esp. in darker skinned individuals)
    3. Atrophy in skin areas directly over bone (eg. forehead)
    4. Neuropathy where nerves are superficial (e.g. elbow)
      1. Paresthesias may persist up to 3 months
  3. Uncommon
    1. Hypertrophic Scar
    2. Alopecia

VIII. Precautions

  1. See contraindications above
  2. Test on only a few lesions at first
  3. Avoid use in young children, especially under age 7 years old (too painful)
  4. Exercise caution in elderly
  5. Exercise caution near bony prominences
  6. Avoid in periungual sites
    1. Excessive pain
    2. Risk of subungual Hemorrhage
    3. Risk of Nail Dystrophy from matrix destruction
  7. Use cautiously near superficial nerves
    1. Especially
      1. Distal sides of the fingertips
      2. Temples (lateral canthus to sideburns)
    2. Risk of nerve injury
    3. Move skin frequently while applying Cryotherapy
      1. Reduces deeper freezing

IX. Anesthesia

  1. Consider EMLA 90 minutes before treatment
  2. Tylenol beforehand also effective

X. Technique

  1. Debulking prior to Cryotherapy
    1. Carefully pare wart with #15 blade or double edge razor blade
    2. Increases chance of success
    3. If bleeding occurs, carefully apply 88% TCA
  2. Isolate lesion
    1. Lifting and pinching lesion between gloved fingers
      1. Reduces pain and increases response
    2. Consider using plastic otoscope nasal speculum tip
      1. Hold over the lesion
      2. Localizes Cryotherapy without spread
    3. Open cone shield
      1. Specific to direct Cryotherapy
      2. Used in similar fashion to otoscope tip
  3. Apply Liquid Nitrogen
    1. Margin sizes
      1. Benign lesion: 1-2 mm margin
      2. Premalignancy: 2-3 mm margin
      3. Malignancy: 4-5 mm margin
        1. Not typically recommended for malignancy without prior biopsy
    2. Cotton or Synthetic Applicator (Dipstick technique)
      1. Sufficient for non-malignant lesions such as warts, molluscum, Actinic Keratoses, Lentigo simplex
        1. Not sufficient for malignant lesions (lesions require a lower Temperature, see above)
      2. Warn about burning pain (lasts 15-30 minutes)
      3. Bulk up cotton applicator with added cotton wisps
      4. Shape or twirl cotton tip to size of wart
      5. Touch cotton tip to wart without pressure
        1. Allow gravity to feed the Liquid Nitrogen
      6. Allow ice ball to extend 1-2mm beyond wart margin
        1. Achieved in 15-45 seconds
      7. Freeze, Allow to Slowly Thaw, and then refreeze
    3. Cryospray unit (Spray gun)
      1. Precautions
        1. Spray unit freezes tissue more rapidly, deeply
        2. Avoid use near eyes, nose or lips
          1. Uncomfortable for patient
          2. Use cotton applicator here instead
        3. When using spray near ear canals
          1. Plug Ear canals with cotton
      2. Technique
        1. Isolate lesion with techniques above
        2. Hold spray tip 1-2 cm from target
        3. Squeeze trigger gently or in brief pulses
        4. Use paintbrush, spiral or rotary technique
        5. Timed spot freeze technique most common
          1. Consider marking desired margin around lesion
            1. See above for recommended margin size
          2. Spray to form margin around lesion
            1. Divide lesion into segments if >2 cm
          3. Maintain constant spray pressure
            1. Keep target frozen for adequate time
            2. Freeze duration may range from 5-30 seconds depending on lesion (see above)
          4. Allow lesion to thaw completely (2-5 minutes)
          5. Repeat freeze-thaw cycle as needed
        6. Cryoblast Technique
          1. Indicated in thick, hyperkeratotic lesions (e.g. Plantar Wart)
          2. Standard spray tip is removed from spray gun and freeze is applied in 1-2 second pulses
          3. Continue until intended ice ball is created
          4. Canpolat (2008) Eur J Dermatol 18(3): 341-2 [PubMed]
    4. Cryoprobe
      1. Small metal probe attached as accessory to spray gun nozzle
        1. Apply gel medium to skin
        2. Cooled metal is applied directly to skin lesions (with gel between metal and skin)
      2. Indications
        1. Small facial lesions
        2. Vascular lesions

XI. Management: Follow-up Care

  1. Antibiotic ointment (Bacitracin) and dressing
  2. Anticipatory Guidance
    1. Pre-printed handouts
    2. Blisters or Hemorrhagic Blisters usually occurs in 12-24 hours
      1. Leave intact (acts as a dressing)
      2. If Tense and painful, it may be drained
  3. Re-evaluation in 2-3 weeks

XII. Efficacy

  1. For Plantar Warts, Cryotherapy was no more effective than home therapy with pumice stone and salicylic acid
    1. Cockayne (2011) BMJ 342: d3271 [PubMed]
  2. Studies showing efficacy compared with Placebo lacking
  3. More aggressive Cryotherapy appears more effective
    1. However, higher risk for complications
  4. References
    1. Gibbs (2002) BMJ 325:461-4 [PubMed]

XIII. Resources

  1. Cryosurgery (Dr. Ursatine)
    1. https://www.youtube.com/watch?v=K7DkK8myhj4&list=PLUNr-W96YAK_6UzGyEL-yAQalBdA7Dnzs&index=2

XIV. References

  1. Hocutt in Pfenninger (1994) Procedures, p. 102-20
  2. Andrews (2004) Am Fam Physician 69:2365-72 [PubMed]
  3. Clebak (2020) Am Fam Physician 101(7): 399-406 [PubMed]
  4. Zimmerman (2012) Am Fam Physician 86(12): 1118-24 [PubMed]

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