Cutaneous Radiation Syndrome

• Definitions
• Clinical information
• Management of cutaneous radiation syndrome
• Radiation physics and skin effects
• Manifestations of acute skin injury
• Manifestations of late/chronic skin injury
• Evaluation of Cutaneous Radiation Syndrome
• Phases of Cutaneous Radiation Syndrome
• Prognosis of Cutaneous Radiation Syndrome
• Gallery of clinical photographs
• Bibliography

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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:
    • 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 known as beta burns.
  • 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 radiation
  • 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 ranges of minimal threshold radiation doses necessary to produce ionizing radiation-induced skin injury (e.g., 3-5 Gy).
  • 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.
  • Consult Bibliography for references.
• Gallery of clinical photographs illustrates "focal" areas of radiation skin injury.
• Extensive skin injury can evolve over time as shown in many colored photos in the article below.
  • Reyes EH, Baciu F, Benderitter M, Lataillade JJ, Bey E, Trompier F, Tamarat R. Medical Response to Radiological Accidents in Latin America and International Assistance. Radiat Res. 2016 Apr;185(4):359-65. [PubMed Citation]
• Radiation-induced skin injury can result from sufficiently high levels of
  • Radiation exposure without external contamination
  • Radiation exposure due to external contamination
  • Both radiation exposure and external contamination
• Skin histologic architecture and burns
  • Illustration of skin anatomy and levels of burn injury
  • Normal skin thickness varies widely (e.g., compare eyelids vs. palms and soles)
  • 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.
• 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 of cutaneous radiation syndrome

• Management of severe radiation skin injuries must be highly individualized.
  • Key management references
    • Iddins CJ, DiCarlo AL, et al. Cutaneous and Local Radiation Injuries. Journal of Radiological Protection. 2022 Jan 12; 42(1): 011001
    • Dainiak N, Gent RN, et al. Literature Review and Global Consensus on Management of Acute Radiation Syndrome Affecting Nonhematopoietic Organ Systems. Disaster Med Public Health Prep. 2011 Oct;5(3):183-201. [PubMed Citation]
    • Muller K, Meineke V. Advances in the management of localized radiation injuries. Health Phys. 2010 Jun;98(6):843-50. [PubMed Citation]
    • Benderitter M, Gourmelon P, Bey E, Chapel A, Clairand I, Prat M, Lataillade JJ. New emerging concepts in the medical management of local radiation injury. Health Phys. 2010 Jun;98(6):851-7. [PubMed Citation]
    • Kagan RJ, Peck MD, Ahrenholz DH et al. Surgical management of the burn wound and use of skin substitutes: an expert panel white paper. J Burn Care Res 2013;34(2):60-79.
    • Triage, Monitoring and Treatment of people exposed to ionising radiation following a malevolent act (PDF - 11 MB) See Chapter J, section 7: Local radiation injuries, pages 282-296. (TMT Handbook Partners, March 2009)
    • Fliedner TM, Friesecke I, Beyrer K. Medical Management of Radiation Accidents: Manual on the Acute Radiation Syndrome. (METREPOL) (PDF - 970 KB) (originally published by Oxford: British Institute of Radiology; 2001) Compendium to the main METREPOL document (PDF - 580 KB)
    • See also:
      • Manage 4 Subsyndromes of Acute Radiation Syndrome - Interactive Tool
      • Burn Triage and Treatment
  • General considerations for acute medical management may include ^A-15, ^A-17, ^C-2, ^E-3, ^E-5, ^H-3
    • Wound cleanliness and debridement
    • Update tetanus immunization
    • Fluid replacement
    • Management of pain
    • Management of pruritis
    • Topical 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
  • Silverlon Wound Contact, Burn Contact Dressings were approved in November 2022 for use for radiation dermatitis and cutaneous radiation injury through dry desquamation.
    • Silverlon is a silver-impregnated, non-adherent wound contact layer that reduces pain during dressing changes, allows evaporation of moisture in the dressing, and reduces wound infections.
    • Updated Silverlon FDA drug label
  • General considerations for management of severe radiation-induced skin injuries in the subacute and chronic healing phase 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.^A-15
    • 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.^E-3
• 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.
  • This graphic illustrates one example of how dose is attenuated in tissue.
  • Since radiation dose is not uniform as it penetrates through skin and deeper tissue, and it is imprecise to describe a Cutaneous Radiation Syndrome "dose" with a single number.
  • Attenuation patterns in tissue differ due to many factors.
• 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.^E-3
• Physical properties of radiation associated with increasing injury severity
  • Total dose: higher dose → more severe damage and faster onset of symptoms
  • Dose rate: faster dose delivery rate → more severe damage and faster onset of symptoms
  • 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

• Signs
  • Erythema and skin edema
    • Similar to sunburn
    • Erythema may appear with or without edema.
  • Blister
  • Epidermal denudation
    • Dry desquamation
    • Moist desquamation
  • Ulceration
    • Especially after high dose skin exposure at high dose rate
  • Hair and nail changes
    • Epilation (may be temporary)
    • Onycholysis (Onychodystrophy)
• Symptoms
  • Pruritis
  • Local dysesthesias

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Manifestations of Late/Chronic Skin Injury

• Dermal atrophy results in permanent loss of skin appendages and structures
  • Xerosis from loss of
    • Sweat glands (apocrine, eccrine)
    • Sebaceous glands
  • Permanent epilation from loss of hair follicles
  • Swelling, local fibrosis, poor wound healing, local necrosis
  • In extreme cases, distal digit loss may develop from obliteration of vascular/lymphatic vessels.
• Skin fibrosis
  • Dermal fibrosis
  • Loss of subcutaneous fat layer
  • ± Deep tissue fibrosis
  • ± Joint contracture and loss of mobility
  • ± Easy skin trauma & slow, impaired healing
• Chronic ulcer ± eschar formation
• Lentiginous (freckle-like) changes; hyper- and hypo-pigmentation
• Telangiectasias & angioma formation
• Keratoses
• Nail and nail bed changes
  • Onycholysis (Onychodystrophy)
  • Subungual splinter hemorrhages
• Skin cancer (rare but reported)
  • Basal cell carcinoma
  • Squamous cell carcinoma

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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.^A-16, ^C-2, ^H-3
  • 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)^*

Prodromal	Latent	Manifest Illness	Possible 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: Dry desquamation, then transition into late effect phase without any other symptoms OR Blistering, moist desquamation, ulcer/necrosis, then transition into late effect phase OR After 2 weeks additional symptoms may occur, e.g epilation or onycholysis (onychodystrophy)	Epilation: transient or permanent depending on dose Pigment changes Onycholysis (onychodystrophy) Fibrosis Telangiectasis Skin Atrophy Cancer Note: Many of these late/chronic effects can appear years to decades later.

^*Adapted from references A-16, E-4, H-3, H-4

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Prognosis of Cutaneous Radiation Syndrome

Prognosis of Cutaneous Radiation Syndrome (CRS)^*

Syndrome Grade	Severity	Prognosis
1	Mild	Recovery likely
2	Moderate	Recovery likely without significant deficit
3	Severe	Recovery likely with deficit
4	Critical	Serious deficit, with reconstruction probably needed in appropriate setting

^*Adapted from references E-4, H-4

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Gallery of Clinical Photographs

Normal skin

1. Normal skin architecture
2. Skin anatomy and levels of burn injury

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. Telangiectasias and epidermal atrophy
6. Telangiectasias and xerosis
7. Telangiectasias and muscle contractures/fibrosis
8. Lentiginous changes in skin
9. Hyperpigmentation, keratoses, and telangiectasias
10. Hyperpigmentation and onychodystrophy
11. Onycholysis (Onychodystrophy)
12. Ulcer
13. Chronic radiation ulcer
14. Tissue necrosis
15. Skin cancer

Submit pictures for use in the gallery

Cutaneous Radiation Injury - Introduction (YouTube - 2:43 minutes) (HHS/CDC)

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Bibliography

A. Overview and clinical articles

1. Medical Management of Radiation Injuries See page 14 for section on cutaneous injury. (IAEA, PAHO, IFRC, 2020)
   • How to manage patients externally exposed in radiation accidents: 10 steps for medical personnel (PDF - 437 KB) (IAEA, 2018), clinical photos and management guidance
2. DiCarlo AL, Bandremer AC, Hollingsworth BA, Kasim S, Laniyonu A, Todd NF, Wang SJ, Wertheimer ER, Rios CI. Cutaneous Radiation Injuries: Models, Assessment and Treatments. Radiat Res. 2020 Sep 16;194(3):315-344. [PubMed Citation]
3. Rios CI, DiCarlo AL, Marzella L. Cutaneous Radiation Injuries: Models, Assessment and Treatments. Radiat Res. 2020 Sep 16;194(3):310-313. [PubMed Citation]
4. Soriano JL, Calpena AC, Souto EB, Clares B. Therapy for prevention and treatment of skin ionizing radiation damage: a review. Int J Radiat Biol. 2019 May;95(5):537-553. [PubMed Citation]
5. Huang A, Glick SA. Genetic susceptibility to cutaneous radiation injury. Arch Dermatol Res. 2017 Jan;309(1):1-10.  [PubMed Citation]
6. Dainiak N, Gent RN, et al. Literature Review and Global Consensus on Management of Acute Radiation Syndrome Affecting Nonhematopoietic Organ Systems. Disaster Med Public Health Prep. 2011 Oct;5(3):183-201. [PubMed Citation]
7. Kagan RJ, Peck MD, Ahrenholz DH et al. Surgical management of the burn wound and use of skin substitutes: an expert panel white paper. J Burn Care Res 2013;34(2):60-79.
8. Muller K, Meineke V. Advances in the management of localized radiation injuries. Health Phys. 2010 Jun;98(6):843-50. [PubMed Citation]
9. Benderitter M, Gourmelon P, Bey E, Chapel A, Clairand I, Prat M, Lataillade JJ. New emerging concepts in the medical management of local radiation injury. Health Phys. 2010 Jun;98(6):851-7. [PubMed Citation]
10. Muller K, Meineke V. Advances in the management of localized radiation injuries. Health Phys. 2010 Jun;98(6):843-50. [PubMed Citation]
11. Balter S, Hopewell JW, Miller DL, Wagner LK, Zelefsky MJ. Fluoroscopically guided interventional procedures: a review of radiation effects on patients' skin and hair. Radiology. 2010 Feb;254(2):326-41. [PubMed Citation]
12. 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]
13. Berger ME, Christensen DM, Lowry PC, Jones OW, Wiley AL. Medical management of radiation injuries: current approaches. Occup Med (Lond). 2006 May;56(3):162-72. [PubMed Citation]
14. Peter RU, Gottlöber P, Heckmann M, et al. Treatment and Follow-up of Patients Suffering from the Cutaneous Radiation Syndrome, from Proceedings of the First International Conference on 'The radiological consequences of the Chernobyl Accident', European Commission and the Belarus, Russian and Ukrainian Ministries on Chernobyl Affairs, Emergency Situations and Health, March 1996, pp 601-605.
15. Hopewell JW. The skin: its structure and response to ionizing radiation. Int J Radiat Biol. 1990 Apr;57(4):751-73. [PubMed Citation]
16. Meineke V. The role of damage to the cutaneous system in radiation-induced multi-organ failure. BJR Suppl. 2005;27:85-99.
17. Peter RU. Cutaneous radiation syndrome in multi-organ failure. BJR Suppl. 2005;27:180-4
18. 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]
19. Peter RU, Cutaneous radiation syndrome: clinical and therapeutic aspects, Radiological Protection Bulletin, 183: 19-25, 1996  

 

B. HHS information

1. Cutaneous Radiation Injury (HHS/CDC, April 4, 2018)
2. Cutaneous Radiation Injury: Fact Sheet for Physicians (HHS/CDC, 5/10/2006)

 

C. Information from international agencies

1. 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)
2. Diagnosis and Treatment of Radiation Injuries (PDF - 202 KB) (IAEA Safety Reports Series No. 2, Vienna 1998)
3. The biological basis for dose limitation in the skin (International Commission on Radiological Protection, ICRP Publication 59, 1992)
4. Erythema and skin injuries (IAEA)

 

D. Basic research

1. DiCarlo AL, Bandremer AC, Hollingsworth BA, et al. Cutaneous Radiation Injuries: Models, Assessment and Treatments [published online ahead of print, 2020 Aug 28]. Radiat Res. 2020;10.1667/RADE-20-00120.1. [PubMed Citation]
2. Rios CI, DiCarlo AL, Marzella L. Cutaneous Radiation Injuries: Models, Assessment and Treatments [published online ahead of print, 2020 Aug 28]. Radiat Res. 2020;10.1667/RADE-20-00132.1. [PubMed Citation]
3. 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]

 

E. Incidents and incident modeling

1. Wang YY, Yu DJ, Zhao TL, et al. Successful Rescue of the Victim Exposed to a Super High Dose of Iridium-192 during the Nanjing Radiological Accident in Nanjing Radiological Accident in 2014, 2014. Radiat Res. 2019;191(6):527-531. [PubMed Citation]
2. Adams TG, Yeddanapudi N, Clay M, Asher J, Appler J, Casagrande R. Modeling Cutaneous Radiation Injury from Fallout. Disaster Med Public Health Prep. 2019;13(3):463-469.  [PubMed Citation]
3. 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]
4. 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]
5. 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]
6. The radiological accident in Yanango (PDF - 3.30 MB) (IAEA, 2000), See pages 30, 31, 35 for excellent clinical photographs of skin effects, as well as other pages with text descriptions of clinical effects.
7. 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]
8. 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.

 

F. Assessing skin dose from radiation contamination and skin decontamination

1. Dubeau J, Heinmiller BE, Corrigan M. Multiple Methods for Assessing the Dose to Skin Exposed to Radioactive Contamination. Radiat Prot Dosimetry. 2017 Apr 28;174(3):371-376. [PubMed Citation]
2. Tazrart A, Bérard P, Leiterer A, Ménétrier F. Decontamination of radionuclides from skin: an overview. Health Phys. 2013;105(2):201-207. [PubMed Citation]

 

G. Skin and radiological protection

1. PAG Manual: Protective Action Guides and Planning Guidance for Radiological Incidents, EPA-400/R-17/001 (PDF - 1.48 MB) (EPA, January 2017)
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. The biological basis for dose limitation in the skin (International Commission on Radiological Protection, ICRP Publication 59, 1992)

 

H. Books and monographs

1. Hall EJ, Giaccia AJ, Radiobiology for the Radiologist, 8th Edition, Wolters Kluwer, Philadelphia, PA, 2018.
2. 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.
3. Fliedner TM, Friesecke I, Beyrer K. Medical Management of Radiation Accidents: Manual on the Acute Radiation Syndrome, pp.27-32. (METREPOL) (PDF - 970 KB) (originally published by Oxford: British Institute of Radiology; 2001) Compendium to the main METREPOL document (PDF - 580 KB)
4. Barabanova AJ: Local Radiation Injury. In: Gusev IA, Guskova AK, Mettler FA Jr, eds.: Medical Management of Radiation Accidents, 2nd ed. Boca Raton, Fl: CRC Press, 2001, pp. 223-240.
5. Proceedings of the First International Conference on 'The radiological consequences of the Chernobyl Accident', European Commission and the Belarus, Russian and Ukrainian Ministries on Chernobyl Affairs, Emergency Situations and Health, March 1996.
6. 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.
7. Rubin P, Casarett GH, Clinical Radiation Pathology. Saunders, Philadelphia, PA, 1968.