Anthrax, Cutaneous

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Diagnosis and reasoning

This 48 year old patient has presented with multiple lesions on his right arm, following an accidental abrasion. Note the progression of the lesions, from simple abrasions, to pruritic papules, to blackened patches of skin suggestive of eschars. Consider also that he is a cattle farmer, with a high risk of exposure to zoonotic infections; thus, several possibilities should immediately spring to mind: ulceroglandular tularaemia, cutaneous anthrax, rickettsialpox, brown recluse spider bite and orf. Ulceroglandular tularaemia is a possibility here, as it typically begins as a tender, pruritic papule, followed by ulceration and necrosis of the base, with ultimate formation of a blackened eschar. Cutaneous anthrax may also present with a similar clinical picture, giving rise to lesions with a black eschar surrounded by an edematous halo. Rickettsialpox is a mite-borne zoonosis, with eschar formation at the site of the bite. However, it is usually associated with mild and self-limiting systemic symptoms and a generalized papulovesicular rash, both of which are not seen here. In addition, rickettsialpox is more associated with an urban setting. The bite of the brown recluse spider may also give rise to an erythematous, pruritic papule, which later breaks down and forms an ulcer with a necrotic base. Note that the bite often passes unnoticed at the start. Orf is a viral disease of sheep and goats. It is transmitted to farmers or meat handlers through direct contact or contaminated fomites. Lesions are seen on fingers and dorsa of the hands in the form of inflamed and later ulcerated papules or nodules. Note that a staphylococcal carbuncle may present in this manner, although the cutaneous lesion would typically be prominently tender. Swabs of the lesions for gram staining and culture are a good initial diagnostic test; the presence of Bacillus anthracis in the isolate establishes cutaneous anthrax as the diagnosis. Given the absence of features suggestive of systemic invasion, blood cultures and lumbar punctures are probably not indicated. Nasal swab tests are not important diagnostically, as their sensitivity is very low. The centers for disease control (CDC) recommend an oral fluoroquinolone or doxycycline in patients with cutaneous anthrax without systemic spread. Note that topical antibiotics have no proven benefit in this setting. A dry dressing is effective in preventing secondary bacterial colonization of the lesion. While raxibacumab, a recombinant IgG monoclonal antibody against the protective antigen of B. Anthracis, has been approved for the treatment of inhalational anthrax, it has not been approved for the management of cutaneous disease - except in the case of systemic spread.


Discussion

Anthrax is a zoonotic infection which can be transmitted to humans via direct contact with a range of wild and domestic animals, including cattle, sheep, goats and horses, or contaminated material and animal products. It is an uncommon disease in much of the world, encountered mostly in farmers, herders, butchers, tanners, woolsorters and others who come into contact with farm animals or animal products. Naturally occurring anthrax is encountered in rural-agricultural regions and is more common in in the Middle East, South Asia, Africa and South/Central America, in comparison to Europe and North America. Anthrax is better known as a biological warfare agent which is particularly lethal. The infection is caused by the bacteria, Bacillus anthracis, a gram positive rod, which forms endospores that are able to survive in the environment for years. The endospores can be introduced into the human body by several means: inhalational, cutaneous and gastrointestinal, giving rise to the three eponymous forms of the disease. Once within the body, the endospores germinate and the dormant bacteria gets activated and begins to multiply. The bacteria are protected by a capsule which aid them in evading the host immune system. Several exotoxins are produced by the bacteria, which are responsible for both the local and systemic manifestations of the illness, as well as for inhibiting the immune response mounted against the organism. Cutaneous anthrax is the commonest form of the disease; the endospores are introduced subcutaneously. Pruritic, painless papules erupt at the initial point of entry several days following the introduction of the organism. In 2 to 3 days, the papules become vesicles that undergo central necrosis followed by drying. This leaves a blackened eschar, which may be surrounded by a halo of oedema. Secondary bacterial infection of the lesion may result in tenderness and a purulent exudate. Gram stain and culture of the base or exudative fluids of the lesion is a valuable initial investigation. The presence of gram positive rods containing central to subterminal spores growing in bamboo-like chains should raise the suspicion of infection with Bacillus species. Cultures of the organism typically reveal characteristic flat, white-grey, nonhemolytic colonies, with comma-shaped outgrowths along the edges. In patients presenting with systemic features, a blood culture may also give positive results. Serological tests may be conducted to detect antibodies against exotoxins or capsular antigen. However, in cutaneous anthrax without systemic invasion, these tests may not be justifiable. They may be used for retrospective confirmation of anthrax infection. Polymerase chain reaction (PCR) testing from culture isolates may aid in the definitive diagnosis, although the test may not be available in many institutions. Oral Ciprofloxacin and doxycycline are recommended for the treatment of adult cutaneous anthrax. If naturally acquired, a 7 to 10 day course of treatment is usually sufficient. If bioterrorism-related or inhalational exposure is suspected, a 60 day course of post exposure prophylaxis is essential, as ungerminated spores may persist in the lungs. Note that ciprofloxacin is the drug of choice in pregnancy and the postpartum period. The intravenous (IV) route should be used in the presence of systemic involvement, and in those cases presenting with extensive edema or lesions in the head and neck, in order to prevent the development of airway compromise. Corticosteroids are indicated in the treatment of life-threatening edema. Dry dressings applied to affected sites help prevent secondary bacterial colonization. Vaccines are indicated in high risk persons: laboratory personnel, persons in contact with animal products, veterinarians and military personnel. The lesions of cutaneous anthrax generally resolve completely, without scar formation. The mortality rate is very low, in comparison to the other forms of anthrax.


Take home messages

  1. The lesions of cutaneous anthrax typically develop as painless papules, which then develop into vesicles which subsequently undergo central necrosis, giving rise to an eschar with a halo of surrounding edema.
  2. Cutaneous anthrax is generally a mild disease, however, early initiation of therapy is important to prevent systemic invasion.
  3. Fluoroquinolones and doxycycline are the drugs of choice in cutaneous anthrax.

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