Cutaneous Manifestations of Biologic, Chemical, and Radiologic Attacks

Cutaneous Manifestations of Biologic, Chemical, and Radiologic Attacks: Introduction

Biologic, Chemical, and Radiologic Terrorism Attacks at a Glance

Potential biologic weapons are classified by the Centers for Disease Control and Prevention into Category A, B, and C levels of risk.
Category A comprises smallpox, anthrax, plague, tularemia, botulism, and viral hemorrhagic fevers.
Category B comprises a large number of pathogens ranging from Brucella and Listeria to the toxins produced by Clostridium perfringens.
Category C comprises a number of viruses, rickettsioses, multidrug-resistant tuberculosis, and rabies.
Chemical weapons are categorized into blistering agents (such as sulfur mustard), nerve agents, blood agents, urticating agents, and incapacitating agents.
Radiologic weapons include what is called a dirty bomb, which produces low levels of radiation contaminating an entire zone.

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.

Public health authorities recognize that terrorism may involve other sorts of unconventional weapons, including chemical and radiologic weapons. This chapter provides an overview of the manifestations of unconventional weapons that terrorists might use.

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.

Table 213-1 Biologic Agents or Diseases Most Likely to Be Used in Terrorism or Warfare (Centers for Disease Control and Prevention and National Institutes of Health Category A Agents or Diseases)a

Disease	Pathogen or Agent	Weaponized Route of Transmission	Cutaneous Findings	Percent with Cutaneous Findings in Bioterror Attack	Chapter in Dermatology in General Medicine
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	—

Table 213-2 Centers for Disease Control and Prevention and National Institutes of Health Category B Agents or Diseasesa

Disease	Pathogen or Agent	Cutaneous Findings	Chapter in Dermatology in General Medicine, 8th Edition
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

Table 213-3 Examples of Centers for Disease Control and Prevention and National Institutes of Health Category C Agents or Diseasesa

Nipah virus
Hanta virus
Tick-borne hemorrhagic fever virus, specifically Crimean–Congo hemorrhagic feverb
Tick-borne encephalitis complex
Yellow feverb
Avian influenza virus and severe acute respiratory syndrome virusc
Multidrug-resistant tuberculosis
Rabies
Other rickettsioses (e.g., those caused by Rickettsia typhi, Rickettsia conori, Rickettsia rickettsia, Orientia tsutsugamushi)

Category A Agents and Diseases

(Table 213-1)

Anthrax

(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.

The Easy Weaponization of This Highly Lethal Agent Makes it One of the Most Feared Biologic Weapons

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.

Anthrax Transmission

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

Clinical Findings

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

Diagnosis

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.

eBox 213-0.1 Diagnostic Algorithm for Suspected Cutaneous Anthrax

The highest suspicion should be given to those lesions in which the patient had a known or highly suspected exposure to anthrax. However, as some of the recent cases have demonstrated, no known exposure had occurred when the patients presented for care.
Notify your local Department of Health to inform them of the patient with suspected anthrax and to obtain any additional instructions before doing diagnostic tests. (A list of state Department of Health contacts can be found at http://www.cdc.gov/phppo by clicking on “State Public Health Locator”). Notify your local laboratory regarding suspected anthrax, and inform them that samples will be sent shortly.
Diagnosis: Physicians should maintain universal precautions when evaluating patients with suspected cutaneous anthrax (mask is not required). Although contact with exudate should be avoided (as should contact with any blood or body fluid), physicians evaluating patients with suspected cutaneous anthrax are not considered at risk for contracting inhalational anthrax because the disease is acquired through contact with anthrax spores, not active bacteria. The laboratory evaluation should include the following:
Swab exudates for Gram stain and culture. The organism is best demonstrated when lesions are in the vesicular stage. If vesicles are present, soak two, dry, sterile Dacron- or Rayon- (not cotton) tipped swabs in vesicular fluid from a previously unopened vesicle. During the eschar stage, gently lift an edge of the eschar and rotate two swabs beneath the edge without removing the eschar. If neither vesicle nor eschar is present, swab the base of the ulcer with a sterile, moist, synthetic (Dacron or Rayon) swab. (Lesions usually become sterile within 24–48 hours after starting antibiotics effective against Bacillus anthracis. Therefore, culture of lesions in patients on antibiotics may not yield bacterial growth.)
Obtain a full-thickness (through the entire dermis), 4-mm punch biopsy for permanent sections (formalin-fixed) for histologic evaluation, IHC studies, and PCR. A second sterile punch biopsy specimen can be obtained for Gram stain and bacterial culture and fungal and atypical mycobacterial stains and cultures if indicated (bacterial Culturette or sterile nonbacteriostatic saline). Dividing a single biopsy specimen is not recommended.
- If a vesicle is present, biopsy the edge of the vesicle and include adjacent nonvesicular skin.
- If an eschar is present, biopsy the erythematous area immediately adjacent to the edge of the eschar. If possible, a second biopsy from the center of the eschar is useful.
- If both a vesicle and eschar are present, a biopsy of each lesion is indicated.
- Submitted specimens should be accompanied by information such as brief clinical history, description, and chronology of the lesion(s), treatment, and date of biopsy in relation to antibiotic treatment. A photograph, digital image, or diagram indicating the site of each biopsy in relation to the lesion and descriptive details of the lesion would be extremely valuable.
- The sample for permanent sections should be placed in formalin and shipped at room temperature. After preparing hematoxylin and eosin-stained slides,a the fixed tissue block should be saved by the dermatopathology laboratory for potential transfer to the CDC for histologic evaluation, IHC, and PCR.
- The sample for culture should be transported immediately to the microbiology laboratory fresh in a sterile container or in a bacterial culture tube (e.g., a Culturette) for immediate processing for Gram stain and bacterial culture, and fungal and atypical mycobacterial stains and cultures if indicated. (One may add sterile nonbacteriostatic saline to the container.)
Draw one 5-mL tube of blood into a red-topped or serum separator tube and transfer it to the laboratory for isolation of serum and subsequent storage of serum at −70°C (−94°F). Label the tube: “Anthrax serology. Store serum at −70°C for special pickup.” A similar convalescent sample should also be drawn 3–4 weeks later.
Draw one 5-mL tube of blood into a purple-topped tube. This tube should be refrigerated and held for pick up for potential PCR diagnostic tests by the CDC. Blood-based assays are currently in a state of development by the CDC. During your contact with your local laboratory or Department of Health office, ask them about the up-to-date blood-testing recommendations.
Obtain blood cultures for febrile or hospitalized patients. There is no need to perform nasal swabs unless directed by the public health authorities as part of an epidemiologic investigation.

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.

Differential Diagnosis

Acute staphylococcal cellulitis with a central pustular lesion or an abscess with a necrotic eschar, particularly those due to methicillin-resistant Staphylococcus aureus

Only gold members can continue reading. Log In or Register to continue