Cutaneous Manifestations of Biologic, Chemical, and Radiologic Attacks: Introduction
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The bombings of the World Trade Center’s twin towers on September 11, 2001, and the spate of anthrax cases that soon followed introduced new responsibilities to the medical and public health communities.1–3 Physicians now have a societal responsibility to know the principles of responding to outbreaks of disease caused by biologic weapons. The dermatologist’s role in recognizing bioterrorism is particularly significant because many pathogens produce illnesses with prominent cutaneous findings.4,5 The dermatologic aspects of smallpox, for example, are the most obvious and dramatic aspects of the disease. Other conditions, such as anthrax, frequently—although not always—manifest in the skin. It is likely that the diagnosis of an index case of a bioterror outbreak will rest on dermatologic findings, subtle or overt.
Biologic Weapons
The Centers for Disease Control and Prevention (CDC) stratified potential bioweapons into three levels of risk (Tables 213-1, 213-2 and 213-3) based on ease of manufacture, ease of dissemination, subsequent person-to-person transmission, lethality, and psychosocial effects (literally, how terrified a community will be). When an organism is intentionally dispersed as part of warfare, terrorism, or criminal activity, a goal is to infect huge numbers of people. Hence, the dispersal system may be engineered to disseminate the disease widely, often as airborne spread that results in pulmonary or inhalational disease. Some—but not all—of the pathogens are then transmissible from person to person, thereby potentiating the public health effects of—and the terror associated with—biologic weapons.
Disease | Pathogen or Agent | Weaponized Route of Transmission | Cutaneous Findings | Percent with Cutaneous Findings in Bioterror Attack | Chapter in Dermatology in General Medicine |
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Smallpox | Variola | Airborne, then person to person. | Enanthem followed by classic vesicopustular eruption. | All | 195 |
Anthrax | Bacillus anthracis | Airborne. No person-to-person transmission. | Edematous papule or plaque evolving into an ulcer surmounted by a black eschar. | Roughly 50%, based on 2001 experience | 183 |
Plague | Yersinia pestis | Airborne, then person to person. | None in pure pulmonary form. Distal purpura and gangrene in septicemic form. Buboes in bubonic form. | Not known | 183 |
Tularemia | Francisella tularensis | Airborne without subsequent person-to-person transmission. | None in pure pulmonary form. Membranous pharyngitis and oropharyngeal ulcers in oropharyngeal form. Ulceroglandular syndrome. | Not known | 183 |
Botulism | Toxin produced by Clostridium botulinum | Airborne, less likely through intentional contamination of food or water. No person-to-person transmission. | Cranial nerve palsies followed by descending paralysis that spares sensation and cognition. Xerostomia, facial palsies, pupils fixed and dilated. | Possibly 100% will have xerostomia, facial palsies, and fixed and dilated pupils | 183 |
Viral hemorrhagic fevers | Examples include filoviruses, such as Ebola and Marburg; arenaviruses, such as Lassa, Junin, and Machupo; flaviviruses, such as dengue; and bunyaviruses, such as hantavirus and Rift Valley fever | Airborne, then possible subsequent transmission depending on agent. Dengue, e.g., is transmitted by the mosquito Aedes aegypti. | Petechiae, purpura, and frank hemorrhage. | Not known | — |
Disease | Pathogen or Agent | Cutaneous Findings | Chapter in Dermatology in General Medicine, 8th Edition |
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Brucellosis | Brucella sp. | 183 | |
Glanders | Burkholderia mallei | 183 | |
Melioidosis | Burkholderia pseudomallei | 183 | |
Typhus | Rickettsia prowazekii | 199 | |
Water safety threats | Examples include bacteria (e.g., Vibrio cholerae), viruses (e.g., Norwalk virus) and protozoa (e.g., Cryptosporidium parvum) | Usually none | |
Food safety threats | Examples include Listeria monocytogenes and Escherichia coli O157:H7 | Rare | |
Psittacosis | Chlamydia psittaci | None | |
Q fever | Coxiella burnetii | None | |
Ricin poisoning | Prepared from Ricinus communis (castor beans) | None | |
Staphylococcal enterotoxin B | None | ||
Viral encephalitis | Examples include α viruses that cause equine encephalitides | Rare | |
Clostridium perfringens toxin | Epsilon toxin of C. perfringens | None |
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(See Chapter 183.) In late 2001, an outbreak of 22 cases in several states along the Eastern Seaboard of the United States was due to an intentional, criminal act of bioterrorism.10,11 The outbreak occurred when envelopes of spores were distributed through the postal system, contaminating many offices and infecting mail handlers and letter recipients. Initially, it was thought the anthrax spores were finely engineered into an easily aerosolized form, but more recent examinations suggest that even crudely milled spores can cause such an outbreak. The Federal Bureau of Investigation now believes that the perpetrator was a scientist working at the US Army’s infectious disease laboratory at Fort Detrick, MD. The motive, however, remains unknown.
During the Cold War, several nations were known to have produced massive quantities of weaponized anthrax, evidence of which became widely known after a 1979 mishap at the Soviet Union’s Sverdlosk bioweapon facility. A cloud of anthrax spores was accidentally released and dozens of people downwind died from inhalational anthrax. The Sverdlosk disaster, however, led to the notion that weaponized anthrax caused only inhalational illness. The letter-borne anthrax incidents of late 2001 showed otherwise when only 11 of the 22 victims had inhalational disease, four of whom died. The others had cutaneous anthrax.
The infectious propagule of Bacillus anthracis is its spore, not the activated bacillus. Under harsh environmental conditions, anthrax bacilli revert into spores that can remain dormant in soil or animal products for decades, impervious to heat, cold, desiccation, and solar radiation. These hardy spores are 1–2 μm in diameter and are easily introduced into open skin, aerosolized and inhaled, or ingested. Once in the hospitable environment of human tissue, the spores germinate, transforming into activated bacilli (2.5 × 10 μm) that generate disease-causing toxins but pose no risk of further direct human-to-human contagion.12
When spores enter the body, they are ingested by host macrophages where they transform into activated bacilli. These macrophages may be carried to regional lymphnodes and produce a hemorrhagic lymphadenitis. If bacteremia ensues, septicemia with shock and often meningitis may follow. The activated bacilli produce exotoxins and virulence factors. A pair of toxins, designated edema toxin and lethal toxin, consists of a pair of noncovalently linked protein components4: edema toxin consists of edema factor (EF) plus protective antigen (PA); lethal toxin consists of lethal factor (LF) plus PA. PA binds to a surface receptor on most mammalian cells and is subsequently cleaved by furin-like proteases. LF is capable of killing macrophages or, at lower concentrations, inducing them to overproduce specific cytokines (TNF-α, interleukin-1β).4 These actions are probably responsible for the sudden death from toxicity that occurs with high concentrations of bacteremia (107–108 bacilli per milliliter of blood) and terminally high lethal toxin levels.13
Inhalational disease can have longer incubation periods than cutaneous disease, perhaps as long as 40–60 days. If a person is on antibiotics (for another reason or for anthrax prophylaxis), Bacillus anthracis may remain in its more protected spore form until the antibiotics are discontinued. The initial symptoms of inhalation anthrax are flu-like and nonspecific, characterized by fever, fatigue, and malaise, but soon followed by chills, high fever, nonproductive cough, and dyspnea. Cyanosis, shock, multiorgan failure, and death may ensue. Chest radiographs characteristically show symmetric mediastinal widening due to hemorrhagic lymphadenitis of mediastinal nodes. In inhalational disease, as well as in septicemic anthrax, which may follow cutaneous or gastrointestinal anthrax, bacteremia may lead to fulminant meningitis.10,11,14,15
Patients with inhalational anthrax often present initially with a flu-like illness that progresses virulently into severe febrile illness accompanied by tachypnea, stridor, and cyanosis. In inhalation anthrax, the chest X-ray shows significant mediastinal widening and hilar adenopathy because of edema and hemorrhagic necrosis of draining nodes. The pulmonary parenchyma is usually spared; hence, the disease is identified as inhalational anthrax, not pulmonary anthrax.12
The acute onset of a painless edematous noduloulcerative lesion with a black eschar should elicit the possible diagnosis of cutaneous anthrax, especially in the epidemiologic setting of exposure to imported animal products, recent travel to endemic areas, or presence of known use of weaponized anthrax (see Fig. 183-1 and eBox 213-0.1).16 An additional clinical clue is the presence of edema vastly out of proportion to the observed size of the cutaneous lesion. Diagnostic steps include obtaining swabs of exudates for Gram stain and culture, biopsy specimens for histopathology and immunohistochemical staining, and to draw blood samples for culture and serology. The CDC requests that practitioners notify local or state health departments before attempting a laboratory diagnosis of cutaneous anthrax.
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The diagnosis is usually suspected on the basis of the character of the lesion and the occupational history, hobby exposure, or likelihood of bioterrorism. Demonstration of large Gram-positive rods in aspirated fluid from beneath the eschar, or on skin punch biopsy, also using a direct fluorescent antibody technique supports the diagnosis. Definitive diagnosis requires culture of the organism and demonstration of its susceptibility to specific bacteriophage lysis. Occasionally, the organism can be isolated from the blood during the acute cutaneous illness as well as in disseminated anthrax. Retrospective serodiagnosis is possible with the demonstration of a titer rise in electrophoretic immunotransblots of antibody to protective antigen and enzyme-linked immunosorbent assay for detection of antibodies to a particular toxin called lethal factor.
Acute staphylococcal cellulitis with a central pustular lesion or an abscess with a necrotic eschar, particularly those due to methicillin-resistant Staphylococcus aureus