The Illinois Department of Public Health is providing the following information about cutaneous anthrax to promote early recognition and reporting of this disease in the event that an individual with possible anthrax seeks medical attention in the state. Health care providers must report suspected or confirmed anthrax cases to their local and state health department immediately (within three hours).

A confirmed case of anthrax, as defined by the U.S. Centers for Disease Control and Prevention (CDC), is 1) a clinically compatible case of cutaneous, inhalational or gastrointestinal illness that is laboratory confirmed by isolation of B. anthracis from an affected tissue or site; or 2) other laboratory evidence of B. anthracis infection based on at least two supportive laboratory tests.

Summary of first four reported bioterrorism cases of cutaneous anthrax

Case 1. This case was a 38-year-old female employee of NBC News who recalled handling a suspicious letter, postmarked September 18, which was eventually determined to contain B. anthracis. On September 25, the patient noted a raised lesion on her chest that developed surrounding edema and erythema over the next three days. By the fourth day of illness, the patient noted malaise and headache. On the sixth day of illness, examination revealed a non-painful non-tender 5 cm oval lesion with a raised border, small satellite vesicles, profound edema, and associated left cervical lymphadenopathy. The initial diagnosis was an infected brown recluse spider bite. The patient was prescribed oral ciprofloxacin. Over the next several days, the lesion developed a black eschar, and a biopsy was obtained and sent to CDC for testing. The tissue was positive by immunohistochemical staining for the cell wall antigen of B. anthracis.

Case 2. This case was a male infant whose mother works for ABC News and who developed a skin lesion on September 29, one day after visiting his mother's office. The left arm lesion was apparently nontender, massively edematous and weeping. He was treated with intravenous antibiotics. Over the next several days, the lesion became ulcerative and developed a black eschar; clinicians presumptively attributed the lesion to a spider bite. The infant's clinical course was complicated by hemolytic anemia and thrombocytopenia, requiring intensive care. The diagnosis of cutaneous anthrax was first considered on October 12 after the announcement of the other confirmed anthrax case in New York City. A serum specimen collected on October 2 was positive for B. anthracis by PCR testing at CDC; a skin biopsy obtained on October 13 was positive by immunohistochemical staining at CDC for the cell wall antigen of B. anthracis. The patient is receiving ciprofloxacin and is improving.

Case 3. This case was a 27-year-old female employee of CBS News. The case-patient had primary responsibility for opening and responding to the mail. The patient did not recall a specific threat letter that may have been the source of exposure. On October 1, she noticed two small papules on her face and, over the next 24 hours, she developed significant facial swelling. Associated symptoms included nausea, diarrhea, sore throat and cervical lymphadenopathy. She was treated empirically with Augmentin® for five days for a presumed infected insect bite. After several days, she developed a blackened eschar. On October 12, after announcement of the NBC case, the patient was reported to the New York City Department of Health and was empirically started on ciprofloxacin. A dermatology consult was obtained, and the skin biopsy was positive by immunohistochemical staining at CDC for the cell wall antigen of B. anthracis and ELISA IgG antibody to protective antigen.

Case 4. This case was a 31-year-old female employee of the New York Post who has primary responsibility for opening and responding to mail. The patient does not recall a specific threat letter that may have been the source of exposure. On September 22, she noticed a "bug bite" on the dorsal aspect of the distal interphalangeal joint of her right finger that was associated with erythema and edema (edema involved the entire digit). Over the next four days, a dark eschar (described as black as coal) began to develop along with associated symptoms of general fatigue and a mild low-grade fever. She was empirically started on amoxicillin/clavulanate on September 28; on October 1, she was evaluated in the emergency department where the wound was debrided but not cultured. She completed a 10-day course of amoxicillin/clavulanate and the ulcer gradually improved. On evaluation October 13, the lesion was described as a shallow, healing ulcer without surrounding erythema or edema.

Clinical Course

Most cases of cutaneous anthrax occur on exposed skin of the arms and hands, less commonly on the face and neck. Cutaneous signs usually begin <1 week and almost always <2 weeks after exposure. The first sign is generally a pruritic papule that can be mistaken for an insect bite. One- to three-millimeter satellite vesicles may appear, and the papule generally progresses over the next one to two days to form a 1-3 cm round, regular ulcer with a necrotic center. This ulcer forms a painless, depressed eschar that loosens and sloughs over the next week or two. Brawny, gelatinous non-pitting edema near the site of inoculation is characteristic and, when present, helps exclude other diseases (see Table 1). Cutaneous anthrax of the eyelid may be complicated by ectropion of the upper lid and corneal scaring resulting in blindness. Lymphangitis and painful lymphadenopathy can occur, as can fever, headache and malaise. Untreated cutaneous anthrax may be associated with malignant edema (facial, neck and upper extremity marked edema and sepsis), septicemia, shock, renal failure and death in 5 percent to 20 percent of cases. Some children have presented with white blood cell counts between 20,000 - 30,000 cells/mm³ and fever of 39C to 40C.

Human-to-human transmission of anthrax has not been documented. Universal precautions should be taken when handling tissue, but there is no cause for undue concern among medical office staff or other patients exposed to a person who is being seen because of a possible B. anthracis infection. Post exposure prophylaxis for these individual should not be needed.

Table 1. Anthrax: Important Differential Diagnosis

Laboratory Diagnosis

A gram stain of vesicular fluid or debrided ulcer base may provide supportive evidence (B. anthracis is a boxcar-shaped encapsulated gram-positive bacillus, whereas the agents of plague and tularemia are gram negative bacilli). Cultures provide confirmatory evidence; laboratories should be informed that B. anthracis is being ruled out in order to ensure that any gram-positive bacillus is speciated. Blood culture should also be performed.

When anthrax is suspected clinically, an unrevealing gram stain does not rule out the diagnosis; the case should be followed closely. The local health department should be contacted immediately and it will assist with arranging testing of the following additional specimens:

• Shallow punch biopsy (fresh-frozen and fixed) for PCR and immunohistochemical staining. This specimen will need to be forwarded through the Illinois Department of Public Health laboratory to the CDC.
• Serum collected from the patient as early as possible in the patient's illness, to aid the eventual serologic confirmation of infection. Serology is only performed by the CDC and such specimens also must be forwarded through the state laboratory. Polymerase chain reaction (PCR) testing also may be performed on blood specimens.

Treatment

The current B. anthracis strains (as of 10/22/01) associated with the intentional exposures are susceptible to ciprofloxacin (500mg BID) and doxycycline (100mg BID), the two drugs approved for post-exposure prophylaxis and recommended as part of initial therapy for inhalational or cutaneous anthrax. Penicillin and amoxicillin are alternatives. The current strains also are susceptible to chloramphenicol, clindamycin, rifampin, vancomycin and clarithromycin, but limited or no data exists regarding the use of these agents in the treatment or prophylaxis of B. anthracis infections. Cephalosporins should not be used for post-exposure prophylaxis or treatment of B. anthracis infections. At least one case of treatment failure with cephalexin (Keflex) has occurred among the recent U.S. cases. Dosing in children is based on weight. Consult with a pharmacist or infectious diseases physician for such dosing information.

Treatment of suspected anthrax should not wait for laboratory confirmation. Patients with anthrax should be evaluated in an inpatient setting to ensure appropriate therapy. Treatment does not prevent the formation of the eschar and topical therapy is not recommended. Edema usually resolves within two to three days of appropriate treatment.

Treatment of cutaneous anthrax should be continued for 60 days "in the setting of bioterrorism, given the presumed exposure to the primary aerosol" (JAMA 1999;281:1735-45). Otherwise the treatment would be indicated for 14 days. Treatment recommendations may change frequently as antibiotic susceptibility results of circulating strains become known. Consultation with an infectious disease clinician is recommended for treatment decisions and consultation with the Morbidity and Mortality Weekly Report (MMWR available at www.cdc.gov) and the CDC bioterrorism Web site (www.bt.cdc.gov) is also advised.

ADDITIONAL RESOURCES

Photographs of Cutaneous Anthrax
Anthrax as a Biological Weapon - JAMA
Anthrax: What Every Clinician Should Know - CDC
Clinical Aspects of Critical Biological Agents: Cutaneous Anthrax - CDC

CDC update for the week of October 19, 2001
Update: Investigation of Anthrax Associated with Intentional Exposure
and Interim Public Health Guidelines - October 19, 2001

Health Department Locator
Illinois Local Health Department Contact Numbers
Other State Health Departments on the World Wide Web