Anthrax differential diagnosis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

The differential diagnosis of anthrax includes a wide range of infectious and non-infectious conditions. Depending on the mode of anthrax exposure in the patient (cutaneous, ingestion, inhalation or injection), there will be different forms of the disease. A history of exposure to contaminated animal materials, occupational exposure, and living in an endemic area, is crucial when considering the diagnosis of anthrax. Additional tests to isolate Bacillus anthracis are required to differentiate anthrax from other diagnoses, thereby confirming the correct etiologic agent.

Differential Diagnosis

Cutaneous Anthrax

• A history of exposure to contaminated animal materials, occupational exposure, and living in an endemic area is crucial when considering a diagnosis of anthrax. A painless, pruritic papule, surrounding vesicles and edema, usually on an exposed region of the body should raise concern of cutaneous anthrax, which is confirmed by the demonstration of Gram-positive encapsulated bacilli on the lesion, and/or positive culture for Bacillus anthracis and/or positive specialized tests.

• The differential diagnosis of the anthrax eschar includes a wide range of infectious and non-infectious conditions, including:

Disease	Findings
Boil (early lesion)	Skin disease caused by the inflammation of hair follicles, thus resulting in the localized accumulation of pus and necrotic tissue. Individual boils may cluster together and form an interconnected network of boils called carbuncles. In severe cases, boils may develop to form abscesses
Arachnid bites	Spider bites can cause allergic reactions. Symptoms of a spider bite may include erythema, pain and edema of the site
Erysipelas	Acute streptococcus bacterial infection of the dermis, resulting in inflammation and characteristically extending into underlying fat tissue. Erythematous skin lesion that enlarges rapidly and has a sharply demarcated raised edge. It appears as a red, swollen, warm, hardened and painful rash, similar in consistency to an orange peel. More severe infections can result in vesicles, bullae, and petechiae, with possible skin necrosis. Lymph nodes may be swollen, and lymphedema may occur. Occasionally, a red streak extending to the lymph node can be seen. The infection may occur on any part of the skin including the face, arms, fingers, legs and toes, but it tends to favor the extremities. Fat tissue is most susceptible to infection, along with facial areas typically around the eyes, ears, and cheeks. Repeated infection of the extremities can lead to chronic lymphadenitis
Glanders	Infectious disease that occurs primarily in horses, mules, and donkeys. It is caused by infection by the bacterium Burkholderia mallei, usually by ingestion of contaminated food or water. Symptoms of glanders include the formation of nodular lesions in the lungs and ulceration of the mucous membranes in the upper respiratory tract. The acute form results in coughing, fever and the release of infectious nasal discharge, followed by septicemia and death within days. In the chronic form, nasal and subcutaneous nodules develop, eventually ulcerating. Death can occur within months, while survivors act as carriers
Plague	Yersinia pestis infection is an infectious disease of animals and humans caused by a bacterium named Yersinia pestis. The typical sign of the most common form of human plague is a swollen and very tender lymph gland, accompanied by pain. The swollen gland is called a "bubo." Bubonic plague should be suspected when a person develops a swollen gland, fever, chills, headache, and extreme exhaustion, and has a history of possible exposure to infected rodents, rabbits, or fleas. A person usually becomes ill with bubonic plague 2 to 6 days after being infected
Syphilitic chancre	Painless ulceration formed during the primary stage of syphilis. This infectious lesion forms approximately 21 days after the initial exposure to Treponema pallidum, the gram-negative spirochaete bacterium yielding syphilis. Chancres transmit syphilis through direct physical contact. These ulcers usually form on or around the anus, mouth, penis, and vagina
Ulceroglandular tularemia	Infectious disease caused by the bacterium Francisella tularensis. Symptoms of tularemia depend on how a person was exposed to the tularemia bacteria. These symptoms can include ulcers on the skin or mouth, swollen and painful lymph glands, swollen and painful eyes, and a sore throat
Rickettsial diseases	Non-motile, Gram-negative, non-sporeforming, highly pleomorphic, obligate intracellular parasites that can present as cocci, rods or thread-like bacteria. May cause conditions, such as the Rocky Mountain spotted fever
Rhizomucor infections	May cause conditions such as Zygomucosis, which causes necrosis of infected tissues and neural invasion. It is a rare disease often found in patients' lungs with a weakeaned immune system which will create a higher fatal outcome
Orf	Or "Sore mouth infection” is a viral infection caused by a member of the poxvirus group and is an infection primarily of sheep and goats. Early in the infection, sores appear as blisters and then become crusty scabs. These may be typically found on the lips or mouth.
Vaccinia	Vaccinia virus infection is very mild and is typically asymptomatic in healthy individuals, but it may cause a mild rash and fever.
Cowpox	Skin disease caused by the Cowpox virus that is related to the Vaccinia virus, also causing a skin rash and fever.
Rat-bite fever	Commonly presents with fever, chills, open sore at the site of the bite and rash, which may show red or purple plaques.
Leishmaniasis	Cutaneous leishmaniasis is characterized by one or more cutaneous lesions. Individuals who have cutaneous leishmaniasis have one or more sores on the skin. The sores can change in size and appearance over time. They often end up looking somewhat like a "volcano", with a raised edge and central depression. A scab covers some sores. The sores can be painless or painful. Some people have swollen glands near the sores.
Ecthyma gangrenosum	Ecthyma gangrenosum is an infection of the skin typically caused by Pseudomonas aeruginosa. It is often seen in immunocompromised patients such as those with neutropenia. Ecthyma gangrenosum presents as a round or oval lesion, 1 to 15cm in diameter, with a halo of erythema. A necrotic center is usually present with a surrounding erythematous edge, representing where the organism invaded blood vessels and caused infarctions. These ulcerous lesions are single or multiple, and heal with scar formation, although sepsis resulting from other gram negative bacteria can also cause this condition.
Herpes	Caused by the Varicella-zoster virus, it commonly starts as a painful rash on one side of the face or body. The rash forms blisters that typically scab over in 7-10 days and clears up within 2-4 weeks.

• Generally these other diseases and conditions lack the characteristic edema of anthrax. The absence of pus, the lack of pain, and the patient’s occupation may provide further diagnostic clues. The outbreak of Rift Valley fever, initially thought to be anthrax in livestock, also affected numerous humans.

• In the differential diagnosis of the severe forms, orbital cellulitis, dacryocystitis and deep tissue infection of the neck, should be considered in the case of severe anthrax lesions involving the face, neck and anterior chest wall. Necrotizing soft tissue infections, particularly group A streptococcal infections and gas gangrene, and severe cellulitis due to staphylococci, should also be considered in the differential diagnosis of severe forms of cutaneous anthrax. Gas and abscess formation are not observed in patients with cutaneous anthrax. Abscess formation is only seen when the lesion is infected with other bacteria, such as streptococci or staphylococci.

Ingestional Anthrax (Oropharyngeal and Gastrointestinal Anthrax)

Oropharyngeal Anthrax

• The list of differential diagnosis of oropharyngeal anthrax includes:

Disease	Findings
Diphtheria	Upper respiratory tract illness characterized by sore throat, low-grade fever, and an adherent membrane (a pseudomembrane) on thetonsils, pharynx, and/or nasal cavity. A milder form of diphtheria can be restricted to the skin. It is caused by Corynebacterium diphtheriae, a facultatively anaerobicGram-positive bacterium
Complicated tonsillitis	Infection of the tonsils which may often cause sore throat and fever. Causes may include adenovirus, rhinovirus, influenza, coronavirus, and respiratory syncytial virus
Streptococcal pharyngitis	Also known as streptococcal sore throat (Strep throat), is a form of group A streptococcal infection that affects the pharynx, and possibly the larynx and tonsils. It may cause Sudden and severe sore throat, red and enlarged tonsils, yellow and white patches in the throat, dysphagia, tender cervical lymphadenopathy, fever, rash and abdominal pain
Vincent's angina	Also known as trench mouth, is a polymicrobial infection of the gums leading to inflammation, bleeding, deep ulceration, necrotic gum tissue, and possibly fever
Ludwig's angina
Parapharyngeal abscess
Deep-tissue infection of the neck

Gastrointestinal Anthrax

• The list of differential diagnosis of gastrointestinal anthrax includes:

Disease	Findings
Food poisoning (in the early stages of intestinal anthrax)
Acute abdomen
Hemorrhagic gastroenteritis
Necrotizing enteritis caused by Clostridium perfringens
Dysentery (amebic or bacterial)

Inhalational Anthrax (Pulmonary, Mediastinal, and Respiratory Anthrax)

• The list of differential diagnosis of inhalation anthrax includes:

Disease	Findings
Mycoplasma pneumoniae
Legionnaires' disease
Psittacosis
Tularemia
Q fever
Viral pneumonia
Histoplasmosis
Coccidiomycosis
Malignancy

Anthrax Meningitis

• Meningitis is a potential complication of anthrax infection. The list of differential diagnosis of anthrax meningitis includes:

Disease	Findings
Acute meningitis
Cerebral malaria
Subarachnoid hemorrhage

• The definitive diagnosis is obtained by visualization of the capsulated bacilli in the cerebrospinal fluid and/or by culture.

Anthrax Sepsis

• Sepsis is a potential complication of anthrax infection.

Disease	Findings
Sepsis

• The definitive diagnosis of anthrax is made by the isolation of Bacillus anthracis from the primary lesion, from blood cultures or by detection of the toxin or DNA of B. anthracis in these specimens.