Differentials
Bacterial furunculosis
SIGNS / SYMPTOMS
Lesions of staphylococcal or streptococcal furunculosis are typically painful, whereas cutaneous anthrax lesions are painless. Bacterial furunculosis may also be suggested by the recurrence of fevers, lymphangitis, and purulent drainage.[32]
INVESTIGATIONS
Wound Gram stain and cultures in bacterial furunculosis should reveal typical pathogens, such as Staphylococcus or Streptococcus.
Ecthyma gangrenosum
SIGNS / SYMPTOMS
Occurs in patients with neutropenia.
INVESTIGATIONS
Blood cultures or tissue cultures will reveal typical pathogens associated with ecthyma gangrenosum, such as Pseudomonas aeruginosa, Staphylococcus, and Candida.
Orf (ecthyma contagiosum)
SIGNS / SYMPTOMS
In cases of orf, a scab forms but the distinctive eschar of cutaneous anthrax is absent. In addition, the notable oedema associated with anthrax does not occur. Cases of orf are distinguished by clinical and historical clues relating to contact with infected sheep or goat flesh.
INVESTIGATIONS
Histological examination of orf reveals epidermal hyperplasia, necrosis, pseudoneoplastic vesicular proliferation, and dermal infiltration with eosinophilic dominance.[62]
Brown recluse spider bite
SIGNS / SYMPTOMS
Brown recluse spider bites are associated with pain, while lesions of cutaneous anthrax are classically painless. In addition, the notable oedema associated with anthrax does not occur. Cases of brown recluse spider bites occur in endemic regions. The brown recluse spider, Loxosceles, can be found in the US in south-eastern Nebraska, Kansas, Oklahoma, Texas, Louisiana, Arkansas, Missouri, Kentucky, Tennessee, Mississippi, Alabama, northern Georgia, and southern portions of Ohio, Indiana, Illinois, and Iowa.[63]
INVESTIGATIONS
Blood or wound cultures would not find Bacillus anthracis.
Influenza infection
SIGNS / SYMPTOMS
Symptoms of malaise, fatigue, low-grade fever, and dyspnoea associated with early inhalation anthrax may resemble influenza. However, coryza, pharyngitis, and nasal congestion do not occur in cases of anthrax.[64]
INVESTIGATIONS
Anthrax cases may be distinguished from influenza by the presence of a widened mediastinum on CXR. Rapid antigen assays and oropharyngeal viral cultures may be useful if positive for influenza.
Mycoplasma pneumonia
SIGNS / SYMPTOMS
Pneumonia and inhalation anthrax may both present with coughing and fever; however, anthrax is differentiated by additional symptoms of loss of consciousness, dizziness, confusion, nausea, vomiting, and shortness of breath (SOB).
INVESTIGATIONS
Blood cultures would not find B anthracis.
Rise in titre of Mycoplasma-specific Ig on convalescent serum.
Positive molecular diagnosis from nasopharyngeal aspirate, sputum, or throat swabs.
Viral pneumonia
SIGNS / SYMPTOMS
Viral pneumonia and inhalation anthrax may both present with coughing and fever; however, anthrax is differentiated by additional symptoms of loss of consciousness, dizziness, confusion, nausea, vomiting, and SOB. Additionally, viral pneumonia may present with sore throat and runny nose, not found with anthrax.
INVESTIGATIONS
Blood cultures would not find B anthracis.
Bronchitis
SIGNS / SYMPTOMS
Bronchitis and inhalation anthrax may both present with coughing; however, anthrax is differentiated by additional symptoms of loss of consciousness, dizziness, confusion, nausea, vomiting, and SOB.
INVESTIGATIONS
There are no specific differentiating tests.
Ruptured aortic aneurysm
SIGNS / SYMPTOMS
Cardiovascular collapse secondary to a ruptured aortic aneurysm may occur alongside a history of cardiovascular disease, high cholesterol, and hypertension, not found with inhalation anthrax.
INVESTIGATIONS
An x-ray shows mediastinal widening much like with a ruptured aortic aneurysm; however, mediastinal changes in anthrax occur early in the infection, along with pulmonary oedema.
Superior vena cava syndrome
SIGNS / SYMPTOMS
Cardiovascular collapse secondary to superior vena cava syndrome must be differentiated from inhalation anthrax.
INVESTIGATIONS
An x-ray shows mediastinal widening much like with superior vena cava syndrome; however, mediastinal changes in anthrax occur early in the infection, along with pulmonary oedema.
Subarachnoid haemorrhage
SIGNS / SYMPTOMS
May be confused with haemorrhagic meningitis; however, anthrax usually has a history of occupational exposure.
INVESTIGATIONS
A subarachnoid haemorrhage may be differentiated from haemorrhagic meningitis on CT scan, Gram stain, and culture of cerebrospinal fluid.
Viral gastroenteritis
SIGNS / SYMPTOMS
Nausea and vomiting may accompany both diagnoses; however, ingestion anthrax often has rebound abdominal tenderness, ascites, oropharyngeal mucosal ulceration, or pseudomembrane formation.[47]
INVESTIGATIONS
Cultures of blood, peritoneal fluid, or oropharyngeal secretions will not yield B anthracis. Standard blood cultures should be sent for laboratory testing. Further confirmatory testing (immunohistochemical staining, gamma phage, polymerase chain reaction [PCR] assays) must be performed by a reference site of the Laboratory Response Network site, if in the US, or according to local protocols in other countries.[37]
Cowpox
SIGNS / SYMPTOMS
Cowpox lesions, characterised by blister formation and scab development resembling eschar, can occur when humans are in direct contact with cowpox ulcers on the cow's udder. Cases are distinguished by historical clues and contact with the affected animal.
INVESTIGATIONS
Specific pathogen PCR testing from a lesion swab can differentiate.
Mpox
SIGNS / SYMPTOMS
Travel history to endemic country or non-endemic country where there is currently a mpox outbreak.
Rash appearance typically evolves from macules to papules, to vesicles to pustules, to crusts. However, lesions may be atypical (e.g., localised to the genital, perineal/perianal, or perioral areas).
INVESTIGATIONS
Specific pathogen PCR testing from a lesion swab can differentiate.
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