Skin reactions caused by nuclear weapons

This material is presented in the textbook on military dermatology Textbook of Military Medicine, which was presented to the editors by Tatyana Svyatenko, professor of the Dnieper Medical University, Doctor of Medical Sciences, member of the EAGV. (Source: Military Dermatology . Translation from English by dermatologist Galina Prit. Photo by Ilja Nedilko on Unsplash).

INTRODUCTION

Throughout the history of warfare, adversaries have constantly used new technologies in an attempt to gain an advantage. In recent history, many countries have focused significant efforts on developing nuclear, biological and chemical weapons to achieve this goal. Although the United States military was aware of the situation, the military medical community was slow to respond to these threats. Accordingly, the research and development of new and more effective drugs, therapeutic approaches, and nuclear, biological, and chemical (NBC) prevention have not received adequate attention.

This problem continues in the field of dermatology. Although basic research has suggested many potential treatments for NBC casualties on the battlefield, the application of all findings to treatment development and treatments has been slow to develop. All military physicians, including dermatologists, must be aware of the NBC threat, know how NBC weapons cause pathology, and use current and potential treatments to care for casualties.

It is clear that many new developments in medicine can be applied to improve current standard treatment regimens for NBC, but to achieve this goal, clinicians must have a clear understanding of the impact of NBC weapons at the clinical and physiological levels, and how these weapons may be used in future wars. To this end, a brief discussion of NBC warfare tactics is presented, clinical data collected over the past 80 years on the effects of NBC weapons are summarized, and the most recent use of mustard gas during the Iran-Iraq War is discussed. Standard treatments for NBC developed during two world wars are explained and new therapeutic regimens based on the latest research are described in detail.

STORY

Some weapons not only deal damage, but can also instill significant fear in the enemy. It is this unique mixture of real and perceived danger that makes nuclear, biological and chemical weapons so attractive.

Nuclear war

The history of nuclear war covers a fairly short period of time, starting with the bombings of Nagasaki and Hiroshima in 1945. Despite the brevity of the nuclear era, it was an extraordinary time in which the ways in which nations related, both politically and militarily, changed dramatically. This situation is explained by the scale of the destructive power of nuclear weapons. The threat of the destruction of global civilization has given leaders of nuclear powers pause when contemplating future conflicts.

The destructive physical power of the atomic bomb in the form of thermal and explosive energy was acutely evident after the atomic bombs were dropped on Japan, but the lasting effects of the radiation were not fully realized until weeks and months after the bombing.

The fact that radiation can cause tissue damage has been known since German physicist Wilhelm Conrad Roentgen discovered X-rays in 1896. Shortly after this discovery, American researcher Thomas Edison observed that his assistant Clarence Dally, who worked with X-rays, developed acute inflammation in his hands, followed by peeling, blistering, ulcers and possible malignancy. This type of effect became evident after the bombing of Hiroshima. Dr. Michihiko Achiya published her diary describing those times. Several passages from his diary clearly describe the evolution of radiation symptoms and the constellation of signs associated with radiation poisoning. The following passage describes the thermal effects of a nuclear explosion (according to Dr. Tabuchi):

“It was a terrible sight,” Dr. Tabuchi said. Hundreds of wounded people, trying to hide in the hills, passed by our house. Looking at them was almost unbearable. Their faces and hands were burned and swollen, and large pieces of skin were torn from their tissues and hung like rags on taxidermy. They moved like a line of ants. They walked past our house all night, but stopped this morning. I saw that they lay on both sides of the road so thickly that it was impossible to pass without stepping on them. However, the sight of the soldiers was worse than the dead people floating on the river... they had no faces! Their eyes, nose and mouth were burned, and their ears seemed to have thawed. It was difficult to tell the difference between front and back. One soldier, whose facial features had been destroyed and his white teeth were left standing out, asked me for water, but I didn’t have any. I clasped my hands and prayed for him. He didn't say anything else. His request for water was probably his last words. Given how burned they were, I was trying to figure out if they were wearing outerwear when the bomb went off.”

Dr. Achiya noted in her notes the following long-term effects of radiation poisoning. “Another observation was that the severity of gastrointestinal symptoms had no relationship to the extent of burns and other injuries. Many patients with severe injuries recovered quickly, while there were patients with the symptoms described who did not appear to be injured at all but nevertheless died. Among those who died, many had bloody diarrhea, similar to that seen in dysentery, and others had bloody urine or sputum. Women often experienced severe uterine bleeding, which we initially took to be a menstrual disorder. Some who stayed a week died from stomatitis or gangrenous tonsillitis. Now that the mortality curve has risen again, stomatitis has appeared, and with it petechiae. The occurrence of petechiae followed the same pattern as we observed in patients with gastrointestinal symptoms. They had nothing to do with the type or severity of the injury, and those who appeared unharmed and were even well enough to help care for other patients began to develop these blood spots under the skin. We have had several cases of apparently healthy people who developed petechiae and died earlier than people who were clearly seriously ill. You can understand what an ominous sign the development of petechiae meant for us.

The events of the nuclear holocaust in Japan forced the leaders of states with nuclear capabilities to avoid the use of nuclear weapons. However, as more countries develop the technological capabilities to create nuclear devices, the threat of a repeat of Hiroshima-like destruction becomes increasingly likely. Therefore, medical professionals must be prepared to treat victims of nuclear war.

NUCLEAR WAR

The types of victims of a nuclear explosion depend on where the explosion occurred, but are always caused by one of three consequences:

• explosive damage (direct and indirect);
• thermal burns;
• radiation injuries.

Thermal and explosive energy accounts for 80% of the energy released by an atomic bomb. A discussion of blast injuries is beyond the scope of this chapter, so we will limit our review to the dermatologic aspects of thermal burns and radiation injuries.

Thermal and radiation effects

Thermal burns may be caused directly by the initial flash of a thermonuclear explosion or by fires secondary to the explosion. Flash burns, caused by radiant or infrared energy from the initial fireball, occur on unprotected skin or under light clothing.

Treatment of thermal burns and blast injuries is significantly complicated by the influence of ionizing radiation. This radiation occurs in the form of neutrons, x-rays, beta particles (electrons), and gamma radiation produced during the first minutes of a nuclear fireball, as well as alpha, beta, and gamma radiation from the residual fallout. Charged alpha and beta particles can penetrate only through the layers of skin, causing initial erythema that can progress to superficial and deep ulcers. Conversely, gamma rays, X-rays and neutrons, all of which have no charge, penetrate deep into the body and can cause severe damage to vital tissues, especially those such as blood-forming tissue with a high rate of cell division. The loss of a significant number of bone marrow cells can lead to an immunosuppressive state in which the affected person is very susceptible to bacterial infections. Additionally, the healing process of the epidermis may be delayed by the same mechanism, resulting in a long recovery period.

The effects of radiation on the human body are divided into several different categories depending on the dose of radiation.

At doses greater than 100-150 councils , patients usually develop radiation hematopoietic syndrome, which, after a latent period of 2-3 weeks, manifests itself as bone marrow suppression, cutaneous and internal hemorrhages and immunosuppression.

At doses of 400 to 1000 councils, gastrointestinal syndrome occurs. This syndrome consists of edema, pseudomembrane formation in the gastrointestinal tract and submucosal hemorrhage in the intestine and is accompanied by prolonged nausea, vomiting, watery diarrhea, shock and death.

At doses above 1000-2000 councils , victims may develop central nervous system disorder syndrome (PCNS) or its cerebrovascular form, which is always fatal. In this syndrome, PCNSL symptoms may occur within minutes, culminating in confusion, prostration, convulsions, and comma. Patients with this syndrome usually die from shock or secondary complications of the PCNSL.

At doses less than 100 councils, the skin is practically unaffected.

At doses of 100 to 200 tips per minute, transient erythema may occur and last for 2 to 3 days. This erythema is thought to be due to vasodilation due to the release of histamine and other vasoactive peptides. Deeper erythema then develops around day 7 and lasts until day 14. Further peeling, suggestive of sunburn, and hyperpigmentation appear in many cases 14 to 21 days after exposure.

Doses from 200 to 1000 tips usually cause epilation within about 1-3 weeks, which at lower doses ( 100-300 tips ) is temporary, and at doses above 700 tips it is permanent. The onset of hair removal may be an indicator of radiation dose, since higher doses cause earlier hair removal. In the range of 700 tips, the amount of losses will be significant.

In case reports of patients receiving high doses of radiation ( 4000–8000 tips ), they describe an acute burning sensation in the skin. In addition, if patients survive for several days, vascular damage in the skin tissue can lead to the formation of diffuse bullae on exposed skin surfaces. The histological picture of skin exposed to high doses of radiation consists of damage to keratinocytes with pyknotic nuclei, severe skin edema and the formation of subepidermal vesicles. At higher doses, endothelial cell edema, intravascular thrombi, and fibrosis are observed.

Skin manifestations that occur over a period of weeks or months, in addition to those noted above, include:

• late erythema, which occurs after 6-8 months and is accompanied by vasculitis, swelling and pain;
• wet peeling, usually appearing after a 3-week period at doses of 1200 to 2000 tips;
• necrosis with an onset of several weeks to months, accompanied by fibrosis, atrophy and proliferation of blood vessels; necrosis occurs at doses greater than 2500 tips.

Systemic effects of ionizing radiation can also occur on the skin. At doses greater than 100 councils, depletion of platelets and their precursors may cause skin petechiae and hemorrhages. Damage to the bone marrow can also lead to immunosuppression, which can lead to an increase in skin infections.

A patient who survives the acute phase of radiation exposure has an increased risk of developing chronic radiation dermatitis and skin neoplasms (delayed effects).

Therapy for radiation skin damage

The involvement of dermatologists in the treatment of thermal injuries following a strategic nuclear attack will certainly be important. The overwhelming number of casualties will quickly overwhelm the capacity of the surgical staff, leaving others to care for burn victims that do not require intensive surgical or burn care. Dermatologists, with their extensive experience and knowledge of skin pathophysiology, are uniquely qualified to care for this type of victim.

Treatment of cutaneous exposure to ionizing radiation remains predominantly symptomatic. The initial step in caring for these patients is decontamination. Sediment particles can cause superficial skin burns but pose a relatively minimal risk of systemic problems. It is important for medical personnel that infection of patients poses little risk to them and should not interfere with appropriate life-saving measures in an emergency situation.

After decontamination , treatment of acute radiation injuries should consist of gentle cleaning and rinsing of exposed blisters, superficial and deep ulcers. As with burns, frequent changes of sterile dressings and antibiotic creams containing sulfadiazine and mafenide are useful in inhibiting local bacterial infections. Careful monitoring for signs of local and systemic infections is of paramount importance since these patients are often immunosuppressed and at increased risk of developing infection.

Because of radiation damage to the gastrointestinal mucosal barrier, these patients are particularly susceptible to intestinal pathogens. For this reason, it has been recommended to prescribe non-absorbable antibiotics to reduce intestinal flora. Additionally, fever of unknown origin should be treated immediately with broad-spectrum antibiotics covering Enterobacteriaceae and Bacteroides fragilis. In irradiated patients who demonstrate an increased potential for Gram-negative organisms as well as avascular ulcers, ciprofloxacin provides moderate coverage of skin infections caused by many Gram-negative organisms, including Enterobacter and Pseudomonas species.

Hydrogel and hydrocolloid gel dressings such as Vigilon and DuoDERM may reduce wound discomfort and wound healing time for radiation ulcers and should be considered if available.

Surgical treatment of chronic, painful non-healing ulcers is often necessary in patients exposed to radiation doses greater than 1000 councils. Surgical removal of necrotic tissue, early treatment of skin infections, and grafting are essential for optimal healing. Because the underlying ulcer often has a compromised blood supply due to vascular damage, the use of pedicle flaps that have an internal blood supply may offer improved recovery (lower graft failure rates).

In the last decade, the study of drugs with clear systemic radioprotective effects has intensified. Animal studies of sulfhydryl drugs such as cysteamine (MEA) have demonstrated that sulfhydryl drugs, both systemic and topical, have a significant radioprotective effect (taken either prophylactically or shortly after exposure) on the acute and late effects of radiation exposure. Histological examination of animals treated with MEA during irradiation showed that there were fewer vascular abnormalities than in unprotected animals. This finding suggests that both acute and late skin changes may be due in part to vascular lesions. A study of radiation therapy patients treated with the hemorheological drug pentoxifylline demonstrated a significant reduction in skin ulcer healing time and pain duration.

Another drug that has a protective effect on animal tissue is cuprozinc superoxide dismutase (CSD). CSD treatment reduces bone marrow cell toxicity from irradiation in mice by half. The exact mechanism by which CSD protects the cell is unclear, but studies have shown that it inhibits the action of poly(ADP [adenosine diphosphate]-ribose) synthetase, which is activated by DNA strand breaks. Poly(ADP-ribose) synthetases, which are activated by DNA breaks, deplete cellular NAD (nicotinamide adenine dinucleotide) and thus deprive the cell of substrates for the production of ATP (adenosine triphosphate), necessary for cell function. Further research on CSD is required to determine its effectiveness in humans. Other researchers have used cytokines to stimulate bone marrow progenitors in patients with radiation syndrome. Interleukin-1 (IL-1), alone and in combination with tumor necrosis factor, IL-6, and colony-stimulating factors, promoted recovery in irradiated mice. In eight patients with bone marrow failure due to cesium-137, the use of granulocyte-macrophage-stimulating factor resulted in a rapid increase in bone marrow granulocytes. Other available drugs that may have a beneficial effect on the course of radiation damage to the skin include antioxidants such as ascorbic acid, α-tocopherol, and butylide hydroxyanisole. (BHA).

Late effects of radiation exposure

Radiation dermatitis and increased susceptibility to skin tumors are late consequences of radiation exposure. The onset of radiodermatitis depends on several variables, including the type of radiation, total dose, duration, and density of radiation. Most clinical experience with the effects of radiation on the skin comes from patients receiving radiation therapy. Patients treated with fractionated radiation therapy in the range of 4000 to 6000 tips experience acute erythema, blistering, necrosis, and desquamation of tissue, leaving an ulcer that heals slowly or does not heal.

Fractionation of the radiation dose allows for high doses of radiation with minimal damage to the skin; therefore, a single high dose exposure may cause significantly more skin damage than a large fractionated dose. Case studies of radiation accident victims reporting that blisters and ulcers can occur in only 1,000 tips support this thesis. Ulcers heal with patchy hyper- and hypopigmentation, atrophic scars, skin fibrosis and telangiectasia. Histologically, chronic radiation injury resembles severe actinic skin damage with epidermal hyperkeratosis, keratinocyte atypia, and elastic changes in the dermis. In addition, changes in skin vessels with thickened walls and thrombosis are observed. Appendages, especially sebaceous glands and hair follicles, which are quite sensitive to ionizing radiation, are often absent. Skin cancers that occur with radiation dermatitis include both squamous cell carcinoma and basal cell carcinoma. These tumors tend to be more aggressive than tumors arising from skin not affected by ionizing radiation.

Therapy for chronic radiation effects of the skin is predominantly palliative. Treatment of chronic ulcers caused by ionizing radiation involves excision and placement of a graft. Vascular changes, thickening of the vessel wall and thrombosis resulting from exposure to ionizing radiation often lead to ischemia, poor healing and an increased risk of infection. Studies on fibroblast cell cultures exposed to ionizing radiation have demonstrated that irradiated fibroblasts have a significantly extended generation time compared to conventional fibroblasts. Therefore, it is important to remove all ischemic, necrotic, and infected tissue, including the ulcer floor and surrounding diseased epidermis, to obtain viable margins on which the graft can be placed.

Other problems associated with radiation-induced skin lesions, especially those involving large areas of skin lesions, include severe pain, hepatorenal failure, and encephalopathic coma. These problems were especially common in the Chernobyl nuclear power plant accident in 1986. Therapy for these patients consists of plasmaphoresis to treat hepatorenal insufficiency and pain medications, including anti-inflammatory drugs and narcotics for pain relief.