Anthrax Differential Diagnoses

Author: Burke A Cunha, MD; Chief Editor: Michael Stuart Bronze, MD more...

Updated: Sep 27, 2011

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Diagnostic Considerations

Early diagnosis is difficult, and a high index of suspicion is required. The differential diagnosis varies among cutaneous, inhalational, and intestinal anthrax.

Cutaneous anthrax

Physicians must differentiate cutaneous anthrax from bubonic plague or lymphocutaneous tularemia. Patients with plague have painful adenopathy, usually in the groin or axilla. No ulcer is present, and ulcer edema and eschar characteristic of anthrax are absent. Patients with bubonic plague appear more toxemic than patients with uncomplicated cutaneous anthrax.

Patients with anthrax have an appropriate history of contact with animal products. In contrast, patients with bubonic plague may have a history of contact with infected cats that may have been in contact with sylvatic rodents in plague-endemic areas. Patients with bubonic plague may also provide a history of contact with armadillos or infected prairie dogs in the western United States.

Inhalational anthrax

Do not confuse inhalational anthrax with the zoonotic atypical pneumonias. Pulmonary tularemia usually presents as a community-acquired pneumonia with bilateral hilar adenopathy and bloody pleural effusion. The primary clinical manifestation of inhalational anthrax is hemorrhagic mediastinitis with bloody pleural effusions. No pulmonary infiltrate is present, and a widened mediastinum is observed on early chest CT scans. Mediastinitis very closely resembles inhalational anthrax on chest radiographs, but their clinical presentations are different.

The initial phase of inhalational anthrax may resemble bacterial mediastinitis, but it is associated with hemoptysis, severe substernal chest pain, and shock, which is very different from bacterial mediastinitis. Patients with bacterial mediastinitis have a history of previous esophageal tear or recent thoracic surgery. Patients with inhalational anthrax have a history of exposure to sources of anthrax spores.

Intestinal anthrax

Intestinal anthrax is a difficult diagnosis that must be distinguished from dysentery. Dysentery may manifest as bloody diarrhea, as does intestinal anthrax, and may be accompanied by abdominal pain (eg, in cases of Shigella or amebic dysentery). A history of ingesting meat possibly contaminated with anthrax is helpful in suspected cases of intestinal anthrax.

In tropical areas where bacillary and amebic dysentery are common, clinically differentiating intestinal anthrax from these endemic causes of dysentery is very difficult unless a cluster of dysentery cases or an outbreak is known to exist. Stool examination provides rapid confirmation of bacillary or amebic dysentery. Stools negative for amebic cysts or trophs and for Shigella suggest the possibility of intestinal anthrax in patients residing near areas where anthrax is endemic (ie, in pastures where herbivores graze) or after ingestion of spores from hand/food contact.

Ulceroglandular tularemia is characterized by purple ulcerative lesions that are painful, not pruritic, and not surrounded by a gelatinous edematous halo. Patients with anthrax, tularemia, or plague may report headache and have fever associated with shaking chills.

The chancre of primary syphilis may also be confused with cutaneous anthrax. The chancre of primary syphilis is painless, as is the lesion of cutaneous anthrax, but the syphilitic chancre is not pruritic and is not surrounded by an edematous halo. Generalized rather than local adenopathy accompanies syphilis, which is the opposite of what is expected with cutaneous anthrax.

Exudates from the ulcers of both ulceroglandular tularemia and cutaneous anthrax reveal organisms when properly stained. The ulcer of syphilis does not reveal organisms, but Treponema pallidum may be visualized using dark-field examination.

Other problems to be considered include the following:

Ecthyma (Pseudomonas aeruginosa and staphylococcal infections)
Glanders (Pseudomonas pseudomallei)
Histoplasmosis
Leprosy
Orf (Rickettsia akari)
Psittacosis
Rat-bite fever (Streptococcus moniliformis, Spirillum minus)
Rickettsia
Tularemia
Typhoid

Differential Diagnoses

Proceed to Workup

Contributor Information and Disclosures

Author

Burke A Cunha, MD Professor of Medicine, State University of New York School of Medicine at Stony Brook; Chief, Infectious Disease Division, Winthrop-University Hospital

Burke A Cunha, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, and Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Ronald A Greenfield, MD Professor, Department of Internal Medicine, University of Oklahoma College of Medicine

Ronald A Greenfield, MD is a member of the following medical societies: American College of Physicians, American Federation for Medical Research, American Society for Microbiology, Central Society for Clinical Research, Infectious Diseases Society of America, Medical Mycology Society of the Americas, Phi Beta Kappa, Southern Society for Clinical Investigation, and Southwestern Association of Clinical Microbiology

Disclosure: Pfizer Honoraria Speaking and teaching; Gilead Honoraria Speaking and teaching; Ortho McNeil Honoraria Speaking and teaching; Abbott Honoraria Speaking and teaching; Astellas Honoraria Speaking and teaching; Cubist Honoraria Speaking and teaching; Forest Pharmaceuticals Speaking and teaching

Chief Editor

Michael Stuart Bronze, MD Professor, Stewart G Wolf Chair in Internal Medicine, Department of Medicine, University of Oklahoma Health Science Center

Michael Stuart Bronze, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American Medical Association, Association of Professors of Medicine, Infectious Diseases Society of America, Oklahoma State Medical Association, and Southern Society for Clinical Investigation

Disclosure: Nothing to disclose.

Additional Contributors

Hilarie Cranmer, MD, MPH, FACEP; Mauricio Martinez, MD; James Li, MD; Barry J Sheridan, DO; Robert G Darling, MD, FACEP

Additional Contributors

Hilarie Cranmer, MD, MPH, FACEP; Mauricio Martinez, MD; James Li, MD; Barry J Sheridan, DO; Robert G Darling, MD, FACEP

References

Inglesby TV, O'Toole T, Henderson DA, et al. Anthrax as a biological weapon, 2002: updated recommendations for management. JAMA. May 1 2002;287(17):2236-52. [Medline].
John TJ, Dandona L, Sharma VP, Kakkar M. Continuing challenge of infectious diseases in India. Lancet. Jan 15 2011;377(9761):252-69. [Medline].
Holty JE, Bravata DM, Liu H, et al. Systematic review: a century of inhalational anthrax cases from 1900 to 2005. Ann Intern Med. Feb 21 2006;144(4):270-80. [Medline].
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].
Knox D, Murray G, Millar M, et al. Subcutaneous anthrax in three intravenous drug users: a new clinical diagnosis. J Bone Joint Surg Br. Mar 2011;93(3):414-7. [Medline].
Food and Drug Administration. 17.5 FDA-Approved Medication Guide. Levaquin (levofloxacin). Accessed August 6, 2009. Available at http://www.accessdata.fda.gov/drugsatfda_docs/label/2009/020634s053,020635s058, 021721s021lbl.pdf.
CDC. Vaccines and Preventable Diseases:Anthrax Vaccination. Vaccines:VPF-VAD/Anthrax/mainpage. Accessed July 9, 2009. Available at http://www.cdc.gov/vaccines/vpd-vac/anthrax/default.htm#vacc.

Polychrome methylene blue stain of Bacillus anthracis. Image courtesy of Anthrax Vaccine Immunization Program Agency, Office of the Army Surgeon General, United States.

Histopathology of mediastinal lymph node showing a microcolony of Bacillus anthracis on Giemsa stain. Image courtesy of Marshall Fox, MD, Public Health Image Library, US Centers for Disease Control and Prevention, Atlanta, Georgia.

Cutaneous anthrax. Image courtesy of Anthrax Vaccine Immunization Program Agency, Office of the Army Surgeon General, United States.

Skin lesion of anthrax on face. Image courtesy of the Public Health Image Library, US Centers for Disease Control and Prevention, Atlanta, Georgia.

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.

Histopathology of large intestine showing marked hemorrhage in the mucosa and submucosa. Image courtesy of Marshall Fox, MD, Public Health Image Library, US Centers for Disease Control and Prevention, Atlanta, Georgia.

Histopathology of the large intestine showing submucosal thrombosis and edema. Image courtesy of Marshall Fox, MD, Public Health Image Library, US Centers for Disease Control and Prevention, Atlanta, Georgia.

Inhalation anthrax. Chest radiograph with widened mediastinum 22 hours before death. Image courtesy of P.S. Brachman, MD, Public Health Image Library, US Centers for Disease Control and Prevention, Atlanta, Georgia.

Histopathology of mediastinal lymph node showing mediastinal necrosis. Image courtesy of Marshall Fox, MD, Public Health Image Library, US Centers for Disease Control and Prevention, Atlanta, Georgia.

Hemorrhagic meningitis resulting from inhalation anthrax. Image courtesy of the Public Health Image Library, US Centers for Disease Control and Prevention, Atlanta, Georgia.

Anthrax infection. Histopathology of hemorrhagic meningitis in anthrax. Image courtesy of Marshall Fox, MD, Public Health Image Library, US Centers for Disease Control and Prevention, Atlanta, Georgia.

Microscopic picture of anthrax showing gram-positive rods. Image courtesy of Ramon E. Moncada, MD.

Bioterrorist Agents. Signs and symptoms. Chart courtesy of North Carolina Statewide Program for Infection Control and Epidemiology (SPICE), copyright University of North Carolina at Chapel Hill, www.unc.edu/depts/spice/bioterrorism.html.

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.

Table 1. Microbiological Differences Between B anthracis and Non– B anthracis Bacilli

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.

Table 2. Toxins and Protein Toxins of Bacillus anthracis

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

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

View Table List