Cutaneous Signs of Bioterrorism

Cutaneous Signs of Bioterrorism

Megan Kinney MHAM, BS

Steven R. Feldman MD, PhD

Jeffrey N. Lackey MD

Scott A. Norton MD, MPH

The world changed on the day we now know as “9/11.” In this new era, physicians in the United States and worldwide have an additional responsibility to know the fundamentals of recognizing and diagnosing an outbreak associated with biologic agents. In this regard, the dermatologist has a particularly important role because most illnesses that arise from biologic agents can have a cutaneous component.

The Centers for Disease Control and Prevention (CDC) has identified six biologic agents as Category A agents, which pose the greatest risk for use in terrorism (Table 47-1). The assessment of risk is based on the ease of production, ease of dissemination, rate of subsequent person-to-person transmission, lethality, and psychosocial effects (literally, how terrified the community will be). These six agents are smallpox, anthrax, botulism, tularemia, plague, and viral hemorrhagic fevers.

In some, for example, smallpox, skin involvement is the most dramatic feature of the disease. In others, cutaneous manifestations are not a central feature, but it is possible, even likely, that the diagnosis of the index case will be made from cutaneous findings, whether they are subtle or obvious. For this reason, an in-depth discussion of the most dermatologically important of these agents, smallpox and anthrax, follows. The other four agents will be briefly discussed high-lighting their cutaneous findings.

Category B and C agents, second- and third-highest priority, respectively, are presented in Tables 47-2 and 47-3.


The patient with smallpox presents a terrible picture, unequalled in any other disease. A picture that fully justifies the horror and fright with which smallpox is associated in the public mind.

William Osler from The Principles and Practice of Medicine

Historical Aspects

The World Health Organization (WHO) regards smallpox, also called variola, as humankind’s deadliest disease. Indeed, smallpox has caused perhaps 10% of all human deaths and, even during its waning years in the 20th century, smallpox killed half a billion people. One third of its victims die. Survivors are usually maimed for life with pocked scars or blindness. Because of the mortality and morbidity associated with smallpox, people long sought ways to prevent, ameliorate, or cure the disease. Fortunately for humankind, smallpox had several characteristics that made it amenable to eradication: there is no subclinical carrier state in humans, the disease is not transmitted by food or water, and there are no animal reservoirs or vectors. The disease occurs only in humans and, during the smallpox era, it was readily diagnosed on a clinical basis alone. A person who survived a bout of smallpox achieved lifelong immunity, but most important, smallpox was preventable through vaccination.

The cowpox vaccine, which Edward Jenner used, and the vaccine that replaced it (one derived from the closely related vaccinia virus) confer near-complete immunity against smallpox. A concerted global vaccination program, led by the health organizations and governments around the world, used the vaccine to quell this disease. The last naturally occurring cases were in Bangladesh and Somalia during the mid-1970s, and a few years later the WHO proclaimed the eradication of smallpox. Shortly afterward, all laboratory stocks of variola virus were destroyed except for a few facilities that maintained small amounts of the virus, putatively for research purposes. There is worrisome speculation, however, that stocks of virus are in unmonitored hands. In addition, the ability to synthesize viral genomes in vitro brings these concerns to a new level as the altered or engineered viral strains could have virulence-enhancing properties. Consequently, there is a risk, at least theoretically, that smallpox might recur. If so, the reappearance of this disease will mark one of the most catastrophic medical, public health, and criminal events that our species has witnessed. For this reason, it is worth bringing smallpox out of the history books and into our current textbooks.

Presentation and Characteristics


Smallpox is caused by the variola virus, a member of the Orthopoxvirus genus within the poxvirus family. This genus also includes cowpox, vaccinia, monkeypox, and a few other viruses that cause mostly nonhuman disease. The poxvirus family has two other genera, one with the familiar molluscum contagiosum, and the other with the zoonotic disorders of orf and milker’s nodules. All members in the poxvirus
family are DNA viruses that replicate within the host cell’s cytoplasm, unlike nearly all other viruses that replicate inside the nuclei.

TABLE 47-1 ▪ CDC Category A Agents: Biologic Agents Most Likely to Be Used in Terrorism or Warfare*



Likely Presentation When Used as a Bioweapon

Cutaneous Manifestations

% of Patients in a Bioterrorism Setting Who Have Cutaneous Manifestations


Variola, an orthopoxvirus

Classic illness described in chapter

Exanthem followed by classic vesiculopustular eruption predominantly on acral surfaces; “pearls of pus”



Bacillus anthracis, an aerobic encapsulated spore-forming gram-positive rod

Inhalational disease starts with flulike presentation and progresses

Edematous papule or plaque evolving into an ulcer surmounted by a black eschar

Roughly 50%


Yersinia pestis,an aerobic gram-negative rod with safety-pin bipolar staining

Fever, weakness, and rapidly developing pneumonia with dyspnea, chest pain, and bloody cough, leading to respiratory failure, shock, and rapid death

Bubonic form from fleabites produces painful tender enlarged lymph nodes (buboes); pneumonic plague may cause DIC with purpura

Not known


Francisella tularensis, an aerobic pleomorphic gram-negative coccobacillus

Hemorrhagic bronchopneumonia with fever

If acquired transcutaneously, then an ulceroglandular or lymphocutaneous presentation

Not known


Toxin produced by the anaerobic gram-positive rod, Clostridium botulinum

Rapid onset of symmetric descending flaccid, paralysis starting in bulbar muscles; afebrile, normal mental status, and no sensory deficits

Facial nerve paralysis, dilated pupils, dry oral mucosa

Presumably most

Viral hemorrhagic fevers

Examples include arenaviruses (e.g., Lassa), filoviruses (Marburg and Ebola)

Flulike illness with fever, myalgias, and extreme fatigue; severe cases have uncontrolled internal and orofacial bleeding

Petechiae, purpura, and hemorrhage

Presumably most

*Biologic warfare is defined as the intentional use of microorganisms or toxins to produce death or disease in humans, animals, or plants.

Abbreviation: DIC, disseminated intravascular coagulation.

Clinical Disease

Smallpox is transmitted primarily in a respiratory manner by droplets from close contact with infected individuals. Fomite transmission, for example, from skin crusts can occur but it is rare. It is feared that weaponized smallpox, on the other hand, will be spread long distances through aerosolization of the virus.

Smallpox has three clinical stages. The first, the incubation phase, starts when a person is initially infected with the virus. Incubation lasts approximately 12 to 14 days (range: 7 to 17 days) and during this time, individuals are unaware that they are infected. They feel well, have no clinical manifestations, and cannot transmit the virus to others. The second stage, the prodrome, begins with a sudden high fever (typically 102°F to 105°F) accompanied by severe headache and backache. During the prodrome, the patient is viremic, appears toxic, is often prostrate with pain, and may be delirious. After 2 to 4 days, the prodrome ends with a slight defervescence and the appearance of an oropharyngeal enanthem. This marks the beginning of the eruptive stage and now the patient is infectious. The classic exanthem has several distinctive features (Fig. 47-1). Individual lesions evolve gradually through several morphologic forms over 14 to 18 days. Lesions progress from macules to papules to vesicles to umbilicated vesicles to pustules to crusted scabs, with each form lasting 1 to 2 days. An important diagnostic feature of
smallpox is that at any one time, all lesions are in the same morphologic stage of development in the region of the body. In contrast, chickenpox lesions progress rapidly and asynchronously; thus, all morphologic forms (e.g., papules, vesicles, pustules, and crusts) are typically present at any moment in the same region of the body.

TABLE 47-2 ▪ Category B Agents: Second-Highest Priority Biologic Agents to Be Used in Terrorism or Warfare

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Likely Presentation When Used as a Bioweapon

Cutaneous Manifestations

Brucellosis (undulant fever)

Brucella species

Flulike symptoms (fever, sweats, headaches, back pains, and physical weakness)

May cause wound infection

Epsilon toxin

Clostridium perfringens

Pulmonary edema leading to renal failure and cardiovascular collapse*


Food safety threats

Salmonella species Escherichia coli 0157:H7 Shigella

GI symptoms “Rose spots” in typhoid fever (Salmonella typhi)


Burkholderia mallei

Pulmonary: malaise, headache, pleurisy

Inoculation nodule and lymphadenitis, ulcerated nodule, mucous membrane ulceration with granulomatous reaction


Burkholderia pseudomallei

Pulmonary: symptoms of mild bronchitis to severe pneumonia, but normal sputum

Bloodstream: Usually affects immunosuppressed patients and leads to septic shock

Chronic Suppurative: Organ abscesses throughout the body

Inoculation through breaks in the skin may form nodule Pustules or subcutaneous abscesses (10-20%); in children, suppurative parotitis


Chlamydia psittaci

Fever, chills, headache, muscle aches, dry cough, pneumonia

Horder spots (pink macules similar to typhoid rose spots), acrocyanosis, superficial venous thrombosis, splinter hemorrhages, erythema multiforme, erythema nodosum

Q Fever

Coxiella burnetti

Pneumonia with nonproductive cough due to aerosolization and inhalation of organism; high fever, vomiting, diarrhea

Occasionally can cause erythema nodosum and erythema annulare centrifugum

Ricin toxin

From Ricinus communis (castor beans)

Inhalation: Sudden onset congestion, respiratory distress (possibly leading to respiratory failure), flulike symptoms (fever, nausea, muscle pain)

Ingestion: mucosal ulceration and hemorrhage leading to severe GI distress; splenic, hepatic, and renal bleeding*,

Allergic reaction: Erythema, vesication, irritation, and pain may occur

Staphylococcal enterotoxin B

From specific strains of Staphylococcus aureus

Inhalation: Flulike symptoms, respiratory distress, chest pain, cough

Ingestion: food poisoning symptoms (nausea, vomiting, abdominal cramping, diarrhea)*,



Rickettsia prowazekii

Malaise, myalgias, headaches, fever, chills; neurologic symptoms such as meningismus and coma may develop

Centrifugally spreading eruption that spares the palms and soles; begins as erythematous, nonconfluent, blanching macules that become maculopapular and petechial

Viral encephalitis

Togaviridae (Eastern equine encephalitis, Venezuelan equine encephalitis, and Western equine encephalitis viruses)§

Flaviviridae (Japanese encephalitis, St. Louis encephalitis, West Nile Virus)

Bunyaviridae, Arenaviridae, Paramyxoviridae

Decreased consciousness, seizures, focal neurologic signs, encephalitis,§ fever, headache, flulike symptoms, nausea, vomiting, diarrhea

Facial/periorbital edema, jaundice, flushing, lymphadenopathy, alopecia, palatal vesicular or petechialeruption, cutaneous morbilliform or petechial eruption may be present

Water safety threats

Vibrio cholerae (cholera) Cryptosporidium parvum (cryptosporidiosis)

Nausea, vomiting, headache, diarrhea (described as rice-water stool in cholera)

Skin infection through open wound and hemorrhagic bullous lesions have occurred with Vibrio, but are very rare

From the CDC Web site unless otherwise indicated.