Anthrax Clinical Presentation
- Author: Burke A Cunha, MD; Chief Editor: Michael Stuart Bronze, MD more...
History
Anthrax is primarily zoonotic. No reports of direct human-to-human transmission exist in the literature, but laboratory personnel may contract the disease from specimens. Exposure to Bacillus anthracis may occur by contact with animals or animal products. Military personnel and civilians may become exposed in biologic warfare situations.
Exposure may be through agriculture or industry. Those at highest risk are shepherds, farmers, and workers in facilities that use animal products, especially previously contaminated goat hair, wool, or bone. Consumers may be exposed through contact with contaminated products (eg, hides in African export shops).
Cutaneous anthrax
Cutaneous anthrax develops 1-7 days (usually 2-5 days) after skin exposure and penetration of B anthracis spores[4] In the most common cutaneous form of anthrax, spores inoculate a host through skin lacerations, abrasions, or biting flies. This form most commonly affects the exposed areas of the upper extremities and, to a lesser extent, the head and neck. (See the images below.) Hematogenous dissemination occurs in 5-10% of untreated cases.
Cutaneous anthrax. Image courtesy of Anthrax Vaccine Immunization Program Agency, Office of the Army Surgeon General, United States. 
Skin lesions of anthrax on neck. Cutaneous anthrax showing the typical black eschar. Image courtesy of the Public Health Image Library, US Centers for Disease Control and Prevention, Atlanta, Georgia. 
Skin lesion of anthrax on face. Image courtesy of the Public Health Image Library, US Centers for Disease Control and Prevention, Atlanta, Georgia. 
Seven-month-old infant with anthrax. In this infant, the infection progressed rapidly with significant edema developing the day after exposure. This large hemorrhagic lesion developed within 3 more days. The infant was febrile and was admitted to the hospital on the second day after the symptoms appeared.On September 28, 2001, the infant had visited the mother's workplace. On September 29, nontender massive edema and a weeping erosion developed. On September 30, a 2-cm sore developed over the edematous area. (Note that edema preceded the primary lesion.) On October 2, an ulcer or eschar formed, and the lesion was diagnosed as a spider bite. Hemolytic anemia and thrombocytopenia developed, and the patient was hospitalized. Serum was drawn on October 2; the polymerase chain reaction results were positive for Bacillus anthracis. On October 13, skin biopsy results were positive with immunohistochemical testing for the cell wall antigen.Note that the initial working diagnosis was a Loxosceles reclusa spider bite with superimposed cellulitis. Courtesy of American Academy of Dermatology with permission of NEJM. 
Fourth patient with cutaneous anthrax in New York City, October 2001. This dry ulcer was present. Photo used with permission of the patient. Courtesy of American Academy of Dermatology. Courtesy of Sharon Balter of the New York City Department of Health. 
Note the hemorrhage that is associated with cutaneous anthrax lesions. The early ulcer has a moist base. Courtesy of American Academy of Dermatology. 
Note the central ulcer and eschar. Courtesy of American Academy of Dermatology. 
An example of a central ulcer and eschar with surrounding edema. Courtesy of American Academy of Dermatology with permission from Boni Elewski, MD. 
Note the black eschar. Courtesy of American Academy of Dermatology. Courtesy of Gorgas Course in Clinical Tropical Medicine. 
Anthrax with facial edema. Courtesy of American Academy of Dermatology. Oropharyngeal anthrax
Oropharyngeal anthrax is a more common form of GI anthrax and has occurred in epidemic settings. For example, ingestion of contaminated water buffalo meat caused an outbreak of 24 cases, concurrently with 52 cases of cutaneous anthrax, in Thailand in 1982.
Ingestion of B anthracis spores may result in oropharyngeal anthrax 2-7 days after exposure. Typically, 2 days after ingestion of contaminated meat, fever and neck swelling occur in the presence of an oral cavity lesion. The lesion starts as an edematous area that becomes necrotic and forms a pseudomembrane within 2 weeks. Sore throat, dysphagia, respiratory distress, and oral bleeding also occur. Soft-issue edema and dramatic cervical lymph node enlargement follow. Recovery usually takes 3 weeks with antibiotic therapy. The reason the disease limits itself to the oropharyngeal area is unknown.
Intestinal anthrax
Intestinal anthrax is a rare form of infection. It occurs from eating infected, undercooked meat. Only 11 cases have been reported, all in underdeveloped countries. Ingesting B anthracis spores may cause intestinal anthrax 2-5 days following ingestion. Abdominal pain and fever occur first, followed by nausea, vomiting, malaise, anorexia, hematemesis, bloody diarrhea, and, less often, watery diarrhea.
Shock may occur from interstitial and intraperitoneal volume losses. Anthrax toxin further causes intrinsic renal failure independent of prerenal azotemia. Death is rapid without antibiotic therapy and aggressive volume resuscitation. The mortality rate is 50%.
Inhalational anthrax
Inhalational anthrax usually occurs in textile and tanning industries among workers handling contaminated animal wool, hair, and hides. Inhalational anthrax begins abruptly, usually 1-3 days (range, 1-60 days) after inhaling anthrax spores, which are 1-5 µm in diameter. The number of spores needed to cause inhalational anthrax varies. As evidenced by anthrax cases in the United States in 2001, fewer spores of weapon-grade anthrax may be required to cause inhalational anthrax.
Patients with inhalational anthrax present initially with nonspecific symptoms, including a low-grade fever and a nonproductive cough. They may report substernal discomfort early in the illness. After initial improvement, inhalational anthrax progresses rapidly, causing hemorrhagic mediastinitis and rapid clinical deterioration. The following symptoms may be present:
- High fever
- Severe shortness of breath
- Tachypnea
- Cyanosis
- Profuse diaphoresis
- Hematemesis
- Chest pain, which may be severe enough to mimic acute myocardial infarction
Septicemic anthrax
Septicemic anthrax refers to overwhelming infection by anthrax bacilli. This form of anthrax may complicate inhalational anthrax. The anthrax bacilli multiply in the blood and proliferate to outnumber red blood cells. Another name for anthrax is black blood, which refers to the very dark color of the blood of animals or humans with overwhelming septicemic anthrax.
Because humans are relatively resistant to invasion by B anthracis, most cases of septicemic anthrax occur following inhalational anthrax. The number of organisms released from the liver or spleen into the bloodstream overwhelms host defenses and produces massive amounts of lethal toxin that cause shock and death.
Physical Examination
Physical findings are nonspecific. The incubation period for all clinical manifestations is 1-6 days following exposure. The prodrome includes fever, malaise, and adenopathy. Inhalational anthrax, the most deadly form, can be mistaken for influenza-like illness, especially during the winter season. Unlike patients with influenza or other viral respiratory illness, adults with inhalational anthrax are not contagious; they will have shortness of breath and vomiting; and they do not have sore throat or rhinorrhea. Subcutaneous anthrax is a subset of cutaneous anthrax that is being recognized more frequently in intravenous drug users. It may also present as necrotizing fasciitis.[5]
Cutaneous anthrax begins as a pruritic papule that enlarges within 24-48 hours to form a 1-cm vesicle and subsequently becomes an ulcer surrounded by an edematous halo.[4] Occasionally, surrounding edema is severe. The cutaneous anthrax lesion is usually approximately 2-3 cm in diameter and has a round, regular, and raised edge.
The skin in infected areas may become edematous and necrotic but not purulent. Such skin lesions have been described as "malignant pustules" after their characteristic appearance, despite being neither malignant nor pustular. The membrane/exudate of the ulcer contains numerous anthrax bacilli. Lesions are painless but on occasion are slightly pruritic. Regional lymphadenopathy of the nodes draining the infected area may occur. The adenopathy associated with cutaneous anthrax may be painful.
The anthrax ulcer and surrounding edema evolve into a black eschar within 7-10 days and last for 7-14 days before separating and leaving a permanent scar. The edema surrounding the ulcer may persist through the eschar stage. Lymphadenopathy associated with cutaneous anthrax may persist long after disappearance of the ulcer/eschar. If the lesions of cutaneous anthrax affect the neck, neck swelling due to edema and enlarged cervical lymph nodes may impinge on the trachea and cause stridor and respiratory distress. Severe cases may result in asphyxiation.
Cutaneous anthrax usually remains localized, but without treatment it disseminates systemically in up to one fifth of cases. Antibiotic therapy prevents dissemination but does not affect the natural history of the lesion.
Oropharyngeal anthrax
Oropharyngeal anthrax is the proximal GI manifestation of intestinal anthrax. Mouth lesions may affect the hard palate or pharyngeal walls. The anthrax ulcer in the oropharynx may be accompanied by a membrane and is associated with local edema and cervical adenopathy. Death may result from asphyxiation due to neck edema or toxemia.
Intestinal anthrax
Patients with intestinal anthrax may have severe abdominal pain, hematemesis, and/or bloody diarrhea. Multiple anthrax ulcerative lesions are found throughout the GI tract secondary to hematogenous spread. Primary intestinal anthrax causes a local lesion that resembles the ulcer of oropharyngeal anthrax. Intestinal anthrax is difficult to recognize, and shock and death may occur 2-5 days after onset.
Inhalational anthrax
The clinical presentation is usually biphasic in nature. The initial stage begins with the onset of myalgia, malaise, fatigue, nonproductive cough, an occasional sensation of retrosternal pressure, and fever. A transient clinical improvement may occur after the first few days.
The second stage, lasting 24 hours and often culminating in death, develops suddenly with the onset of acute respiratory distress, hypoxemia, and cyanosis. The patient may have mild fever; alternatively, the patient may have hypothermia and develop shock.
Diaphoresis often is present; enlarged mediastinal lymph nodes may lead to partial tracheal compression and alarming stridor. Auscultation of the lungs is remarkable for crackles and signs of pleural effusions. Meningeal involvement may be present in up to 50% of cases; it usually is bloody and may be associated with subarachnoid hemorrhage. Decreased level of consciousness, meningismus, and coma may be present. Inhalational anthrax is usually fatal; the patient often succumbs to shock and to the effects of lethal toxin.
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Akbayram S, Dogan M, Akgün C, et al. Clinical findings in children with cutaneous anthrax in eastern Turkey. Pediatr Dermatol. Nov-Dec 2010;27(6):600-6. [Medline].
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| B anthracis | Non–B anthracis bacilli (pseudoanthrax bacilli) |
| Nonmotile long chains | Generally motile short chains |
| Capsule formation on bicarbonate agar | No capsule formation in bicarbonate |
| No growth on penicillin agar (10 mcg/mL) | Usually good growth on penicillin agar |
| Growth in gelatin resembles inverted fir tree | Growth in gelatin absent or resembles atypical fir tree |
| Gelatin liquefaction slow | Gelatin liquefaction usually rapid |
| No hemolysis of sheep RBCs | Hemolysis of sheep RBCs |
| Ferments salicin slowly or not at all | Usually ferments salicin rapidly |
| Pathogenic to laboratory animals | Nonpathogenic to laboratory animals |
| Adapted from Cunha CB. Anthrax: Ancient Plague, Persistent Problem. Infect Dis Pract. 1999;23(4):35-9. | |
| Edema factor (EF) + lethal factor (LF) = Host cell penetration by B anthracis |
| EF + protective antigen (PA) = Edema toxin |
| LF + PA = Lethal toxin (primary virulence factor of B anthracis) |
| Edema toxin + lethal toxin = Inhibited PMN function and phagocytosis |
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