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Cutaneous Radiation Syndrome



Definitions


  • Cutaneous Radiation Syndrome (CRS)
    • One of the four subsyndromes of Acute Radiation Syndrome (ARS)
    • Clinical continuum of pathophysiological reactions of the skin and skin appendages to significant levels of ionizing radiation after: 24
      • Exposure of the skin from whole or partial body radiation which penetrates deeply into tissues (e.g., gamma, neutron)
      • Exposure of very large areas of skin from high energy beta radiation, which usually does not penetrate deeply enough in tissue to cause the 3 other subsyndromes of ARS (hematopoietic, gastrointestinal, neurovascular) but can cause major skin effects
    • Phases of CRS are the same as for the other 3 ARS subsyndromes
      • Prodromal
      • Latent
      • Manifest Illness
      • Recovery (± with chronic or late effects)
    • CRS in this context represents Cutaneous Radiation Syndrome, not Chronic Radiation Syndrome, which has also been called CRS.
  • Cutaneous Radiation Injury (CRI)
    • Clinical continuum of pathophysiological reactions of the skin and skin appendages to significant levels of ionizing radiation24
    • Differences between CRS and CRI
      • CRI need not occur in the context of ARS.
      • CRI may occur when radiation injury (from therapeutic or unintentional exposure) is more localized or if radiation dose is insufficient to penetrate to deeper organs and cause ARS.
      • CRS and CRI may be confused or used interchangeably (though incorrectly) in the medical literature
    • Synonyms of CRI
      • Radiodermatitis
      • Radiation dermatitis
      • Cutaneous radiation effects
    • Phases of CRI
      • Acute
      • Subacute
      • Chronic
      • Late
  • Threshold dose
    • Medical literature provides wide range of minimal threshold radiation doses necessary to produce ionizing radiation-induced skin injury (e.g., 350 - 500 cGy).
    • Intrinsic biological (i.e., host) and inherent physical (i.e., radiation) factors may raise or lower dose required to cause skin injury, therefore no value or value range is provided by REMM.
    • Consult Bibliography for references.

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Clinical information


  • This section provides a brief overview.
  • Gallery of clinical photographs illustrates "focal" areas of radiation skin injury.
    • More extensive skin injury is possible, but not illustrated here.
  • Radiation-induced skin injury can result from sufficiently high levels of
  • Skin histologic architecture
    • Varies widely (e.g., compare eyelids vs. palms and soles)
    • Variables within normal skin architecture include
      • Depth/thickness of epidermis and dermis
      • Density of blood vessels and lymphatics
      • Presence/density of skin appendages (e.g., sweat & sebaceous glands, hair follicles)
    • Differences in skin architecture partially explain how/why tissues differ in response to same/similar radiation doses.
  • Timing of injuries
    • In general, early effects of ionizing radiation-induced skin injury manifest in the epidermis, whereas late effects appear in the dermis.9
  • Radiation burns differ from thermal or chemical burns in various ways including
    • Thermal or chemical burn injuries evolve immediately following insult to skin.
    • Ionizing radiation-induced skin injuries carry a small but real potential for malignancy as a late effect.
    • Chronic scarring patterns differ.
    • See burn information

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Management considerations


  • Management of severe radiation skin injuries must be highly individualized.
    • Consult Bibliography for references.
    • General considerations for acute medical management may include 4, 5, 6, 12, 13, 20, 23
      • Wound cleanliness and debridement
      • Fluid replacement
      • Management of pain
      • Management of pruritis
      • Anti-inflammatory therapy, e.g. corticosteroids
      • Anti-microbial prophylaxis and therapy
      • Inhibitors of proteolysis
      • Growth factors to enhance granulation and re-epithelialization
      • Stimulation of local blood supply, e.g. pentofylline
    • General considerations for management of severe subacute or chronic radiation-induced skin injuries that heal poorly or fail to heal may include
      • Medical therapy
        • Anti-coagulation to prevent clotting in dermal and subcutaneous vessels
        • Anti-inflammatory therapy
        • Range of motion exercises for joints and soft tissues after skin injuries than have re-epithelialized
      • Surgical Therapy
        • Local excision
        • ± Grafting for closure
        • ± Amputation (e.g., digits, limbs)
  • CRS complicates management and recovery from other ARS subsyndromes.
    • CRS (and loss of intact skin barrier) can result in
      • Major microbial infection
      • Bleeding
      • Fluid loss
      • Pain
    • Significant CRS may complicate the radiation-induced multi-organ failure associated with ARS.12
      • After the Chernobyl nuclear reactor accident in the Ukraine 1986, beta burns were the primary cause of death in a number of patients, increasing the morbidity and mortality of ARS, especially when skin injury exceeded 50% of the body surface area.13
  • Significant ionizing radiation-induced skin injury will complicate management and impair healing of co-located physical trauma.
  • Burn specialists will usually assist the radiation response team in management of severe ionizing radiation-induced skin injury.
  • Subsequent trauma to previously irradiated skin is likely to heal slowly/poorly.

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Radiation physics and skin effects


  • With some exceptions, radiation dose decreases (attenuates) as it passes through skin and deeper tissues.
  • Beta burns
    • Represent the effects of beta radiation on the skin.
    • Radiation effects on skin may be significant, but effects rarely go deeper, due to the physical properties of the beta radiation.
    • Nevertheless, widespread beta burns can increase morbidity and mortality of ARS when ARS develops after significant whole body gamma or neutron radiation in addition to the beta burns.13
  • Physical properties of radiation associated with increasing injury severity
    • Total dose: higher dose → more severe damage
    • Dose rate: faster dose delivery rate → more severe damage
    • Extent of area affected: larger/wider area → worse effects
    • Dose depth: deeper dose → more severe damage
    • Radiation with higher RBE → more severe damage

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Manifestations of Acute Skin Injury


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Manifestations of Late/Chronic Skin Injury


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Evaluation of Cutaneous Radiation Syndrome


  • Specialized tests may be helpful in managing selected cases with poorly characterized or severe skin injury.4, 5, 21, 23
    • Sequential color photography: to document skin changes over time
    • Ultrasonography and/or MRI: to evaluate injury depth
    • Thermography: tissue necrosis lowers skin temperature while inflammation raises skin temperature
    • Capillary microscopy: to assess severity of injury by viewing vessels in dermal stratum papillae
    • Profilometry: to evaluate changes to skin surface
    • Histology/biopsy

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Phases of Cutaneous Radiation Syndrome


Phases of Cutaneous Radiation Syndrome (CRS)*

ProdromalLatentManifest IllnessPossible Chronic/Late Effects
  • Erythema
  • Edema
  • Pruritis, increased skin temperature, dysesthesias
  • Variable time, longer duration with lower dose
  • Prodromal symptoms may stabilize or slightly improve
Early:
  • Second wave of erythema, swelling and edema of skin and subcutaneous tissues, corresponding to the renewal of epidermal cells
Later:

Note: Many of these late/chronic effects can appear years to decades later.
*Adapted from references 5, 21, 14, 25

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Prognosis of Cutaneous Radiation Syndrome


Prognosis of Cutaneous Radiation Syndrome (CRS)*

Syndrome GradeSeverityPrognosis
1MildRecovery likely
2ModerateRecovery likely without significant deficit
3SevereRecovery likely with deficit
4CriticalSerious deficit, with reconstruction probably needed in appropriate setting
*Adapted from references 14, 25

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Gallery of Clinical Photographs

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Clinical photographs of cutaneous radiation syndrome (11 MB, requires Flash Player)
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Normal skin
  1. Normal skin architecture
Acute effects:
  1. Erythema and skin edema
  2. Epilation
  3. Blister
  4. Dry desquamation
  5. Moist desquamation
Evolution of skin effects:
  1. Patient OAF in Goiania incident, 1987 -
    blister, evolution to moist desquamation
  2. Peruvian patient exposed to Iridium-192 -
    blister, moist desquamation, ulcer progressing to tissue necrosis
  3. Wife of the Peruvian patient exposed to Iridium-192 -
    Dry desquamation, necrosis, fibrosis, and telangiectasia
  4. Patient involved in a x-ray diffraction accident, 9-96 days postexposure -
    erythema, telangiectasias, blisters, desquamation, cellulitis
Chronic effects:
  1. Skin atrophy
  2. Chronic radiation dermatitis
  3. Fibrosis, contractures, and keratoses
  4. Keratosis and fibrosis
  5. Telangiectases and epidermal atrophy
  6. Telangiectases and xerosis
  7. Telangiectases
  8. Telangiectases and muscle contractures/fibrosis
  9. Lentiginous changes in skin
  10. Hyperpigmentation, keratoses, and telangiectases
  11. Hyperpigmentation and onychodystrophy
  12. Onycholysis (Onychodystrophy)
  13. Ulcer
  14. Chronic radiation ulcer
  15. Tissue necrosis
  16. Skin cancer

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Bibliography


  1. Barabanova A, Baranov A, Bushmanov A, Guskova A , Radiation injuries in humans, Slovo Publishers, Moscow, Russia, 2007. (Russian language)
  2. Charles MW. The skin in radiological protection--recent advances and residual unresolved issues. Radiat Prot Dosimetry. 2004;109(4):323-30. [PubMed Citation]
  3. Cutaneous Radiation Injury: Fact Sheet for Physicians (HHS/CDC, 5/10/2006)
  4. Diagnosis and Treatment of Radiation Injuries (PDF - 202 KB) (IAEA Safety Reports Series No. 2, Vienna 1998)
  5. Fliedner TM, Friesecke I, Beyrer K, eds., Medical management of radiation accidents, Manual on the acute radiation syndrome, British Institute of Radiology, 2001, pp.27-32.
  6. Gottlöber P, Bezold G, Weber L, Gourmelon P, Cosset JM, Bahren W, Hald HJ, Fliedner TM, Peter RU. The radiation accident in Georgia: clinical appearance and diagnosis of cutaneous radiation syndrome. J Am Acad Dermatol. 2000 Mar;42(3):453-8. [PubMed Citation]
  7. Gottlöber P, Steinert M, Weiss M, Bebeshko V, Belyi D, Nadejina N, Stefani FH, Wagemaker G, Fliedner TM, Peter RU. The outcome of local radiation injuries: 14 years of follow-up after the Chernobyl accident. Radiat Res. 2001 Mar;155(3):409-16. [PubMed Citation]
  8. Gusev, IA, Guskova AK, Mettler FA, eds., Medical Management of Radiation Accidents, 2nd Edition, University of New Mexico, Albuquerque, New Mexico, 2001.
  9. Hall EJ, Giaccia AJ, Radiobiology for the Radiologist, 6th Edition, Lippincott Williams & Wilkins, Philadelphia, PA, 2006, pp.333-6.
  10. Hopewell JW. The skin: its structure and response to ionizing radiation. Int J Radiat Biol. 1990 Apr;57(4):751-73. [PubMed Citation]
  11. How to recognize and initially respond to an accidental radiation injury - images of radiation skin effects and injury (poster, PDF - 436 KB) (pamphlet, PDF - 322 KB) (Radiation dermatological injuries, IAEA, WHO)
  12. Meineke V. The role of damage to the cutaneous system in radiation-induced multi-organ failure. BJR Suppl. 2005;27:85-99. [PubMed Citation]
  13. Mettler FA Jr, Guskova AK, Gusev I. Health effects in those with acute radiation sickness from the Chernobyl accident. Health Phys. 2007 Nov;93(5):462-9. [PubMed Citation]
  14. Medical Management of Radiation Accidents, Fred A. Mettler, Angelina K. Guskova, Igor A. Gusev (Eds), 2nd Edition, University of New Mexico, Albuquerque, New Mexico, 2001.
  15. Müller K, Meineke V. Radiation-induced alterations in cytokine production by skin cells. Exp Hematol. 2007 Apr;35(4 Suppl 1):96-104. [PubMed Citation]
  16. Oliveira AR, et al., Skin lesions associated with the Goiania accident, in The Medical Basis for Radiation Accident Preparedness II, 173-181, Ricks RC, Fry SA (eds.), 1990.
  17. Peter RU, Braun-Falco O, Birioukov A, Hacker N, Kerscher M, Peterseim U, Ruzicka T, Konz B, Plewig G. Chronic cutaneous damage after accidental exposure to ionizing radiation: The Chernobyl experience. J Am Acad Dermatol. 1994 May;30(5 Pt 1):719-23. [PubMed Citation]
  18. Peter RU, The Cutaneous radiation syndrome, in Advances in the Treatment of Radiation Injuries/Advances in the Biosciences , MacVittie TJ, Weiss JF, Browne D (eds.), 94:237-40, 1994.
  19. Peter RU, Cutaneous radiation syndrome: clinical and therapeutic aspects, Radiological Protection Bulletin, 183: 19-25, 1996
  20. Peter RU, Gottlöber P. Management of cutaneous radiation injuries: diagnostic and therapeutic principles of the cutaneous radiation syndrome. Mil Med. 2002 Feb;167(2 Suppl):110-2. [PubMed Citation]
  21. Peter RU. Cutaneous radiation syndrome in multi-organ failure. BJR Suppl. 2005;27:180-4. [PubMed Citation]
  22. Peter RU, Management of skin injuries in radiation accidents: The cutaneous radiation syndrome, in The Medical Basis for Radiation-accident Preparedness, the Clinical Care of Victims, Proceedings of the Fourth International Radiation Emergency Assistance Center/Training Site (REAC/TS) Conference, March 2001, Parthenon Publishing Group, New York, NY, 2002.
  23. Radiation Emergency Assistance Center/Training Site, Oak Ridge Institute for Science and Education, Oak Ridge, TN, Advanced Radiation Medicine Course, September 17-21, 2007.
  24. Rubin P, Casarett GH, Clinical Radiation Pathology. Saunders, Philadelphia, PA, 1968.
  25. Steinert M, Weiss M, Gottlöber P, Belyi D, Gergel O, Bebeshko V, Nadejina N, Galstian I, Wagemaker G, Fliedner TM, Peter RU. Delayed effects of accidental cutaneous radiation exposure: fifteen years of follow-up after the Chernobyl accident. J Am Acad Dermatol. 2003 Sep;49(3):417-23. [PubMed Citation]
  26. The biological basis for dose limitation in the skin (International Commission on Radiological Protection, ICRP Publication 59, 1992)
 

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