Anthrax natural history, complications and prognosis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: João André Alves Silva, M.D. [2]

Overview

The natural history of anthrax depends on the mode of anthrax exposure in the patient (cutaneous, ingestion, inhalation, injection). In cutaneous anthrax, a small painless skin sore develops into a blister and later into a skin ulcer, with a black area at the center. The resolution of the lesion takes several weeks and the time to resolution depends on the size, location and local severity of the lesion. The anthrax lesions might lead to scarring and contractures. Inhalation anthrax is characterized by a mild initial phase of nonspecific symptoms that is followed by the sudden development of dyspnea, cyanosis, disorientation with coma, and death. In oropharyngeal anthrax, the lesion is generally localized in the oral cavity. The illness in oropharyngeal anthrax may progress rapidly, and edema around the lymph node may result in extensive swelling of the neck and anterior chest wall. The gastrointestinal anthrax lesions may occur anywhere within the gastrointestinal tract and they may bleed leading to fatal hemorrhage. Some cases are complicated with massive ascites and this leads to shock and death. The prognosis in anthrax depends on the type of anthrax, how early the anthrax is diagnosed, the strain of the bacteria, and the patient's age and health condition. The pulmonary anthrax is the one with highest mortality rate.

Natural History

Cutaneous Anthrax

The incubation period of anthrax ranges from as little as 9 hours to 3 weeks, mostly 2 to 6 or 7 days. The natural history of cutaneous anthrax is shown below.

Day 0

• There is entry of the infecting B. anthracis (usually as spores) through a skin lesion (cut, abrasion, etc.) or (possibly as vegetative forms or vegetative forms and spores) by means of a fly-bite.

Days 2-3

• A small pimple or papule appears.

Days 3-4

• A ring of vesicles develops around the papule. Vesicular fluid may be exuded. Unless the patient was treated, capsulated B. anthracis can be identified in appropriately stained smears of this fluid, and the bacterium can be isolated by culture.
• Marked edema starts to develop.
• Unless there is secondary infection, there is no pus and pathognomonically the lesion itself is not painful, although painful lymphadenitis may occur in the regional lymph nodes and a feeling of pressure may result from the edema.
• The lesion is usually 1-3 cm in diameter and remains round and regular. Occasionally a lesion may be larger and irregularly shaped.

Days 5-7

• The original papule ulcerates to form the characteristic eschar.
• Edema extends some distance from the lesion.
• Systemic symptoms are low-grade fever, malaise, and headache.
• The cutaneous reaction is more exacerbated particularly in cases where it is located on the face, neck, or chest. Clinical symptoms may be more severe in this case, with extensive edema around initial lesion, toxemia, change in mental status, high fever, hypotension, regional lymphadenomegaly, affecting the patient's ability to eat or drink.
• Tracheotomy is a life-saving procedure in patients who have a cutaneous lesion on the face or neck, with extensive edema leading to compression of the trachea. This clinical manifestation is very dangerous.

Day 10

• The eschar begins to resolve; resolution takes several weeks and is not hastened by treatment.
• Clinicians unaware of this suffer from concern that the treatment has been ineffective.
• A small proportion of untreated cases (20%) develop sepsis or meningitis with hyperacute symptoms.

Time to Resolution

• Time to resolution will depend on the size, location and local severity of the lesion.
• The initial crust is separated several weeks after the onset, with subsequent healing by granulation. Sometimes the separation of the crust is delayed, and the lesion may become secondarily infected. In this situation, the crust should be excised surgically.
• Lesions characterized by “malignant edema” can take months to heal.
• Very large lesions may require skin grafts, and lesions in locations such as the eyelid may require surgical intervention due to scarring.

Shown below are images of the development and resolution of uncomplicated cutaneous anthrax lesion.

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  Day 1 of development and resolution of uncomplicated cutaneous anthrax lesion.”Adapted from World Health Organization (WHO)

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  Day 2 - 3 of development and resolution of uncomplicated cutaneous anthrax lesion.”Adapted from World Health Organization (WHO)

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  Day 4 of development and resolution of uncomplicated cutaneous anthrax lesion.”Adapted from World Health Organization (WHO)

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  Day 6 of development and resolution of uncomplicated cutaneous anthrax lesion.”Adapted from World Health Organization (WHO)

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  Day 11 of development and resolution of uncomplicated cutaneous anthrax lesion.”Adapted from World Health Organization (WHO)

Inhalation Anthrax

Initial Phase

• Symptoms prior to the onset of the final hyperacute phase are nonspecific, and suspicion of anthrax depends on the knowledge of the patient’s history. The mild initial phase of nonspecific symptoms is followed by the sudden development of dyspnea, cyanosis, disorientation with coma, and death.

• The typical clinical course of this form of the disease is consistent with the lesion development within the mediastinal lymph nodes before the development of bacteraemia. The assault on the lung appears to be two-pronged. In the initial phase, the blockade of the lymphatic vessels develops, in association with symptoms such as a sensation of tightness of the chest. Lymphatic stasis is associated with edema, which may be apparent above the thoracic inlet, and pleural effusion. Histological sections of the lung may reveal bacilli within the lymphatic vessels. In the acute phase, damage associated with septicemia occurs.

• Lymphatic stasis resulting from the damaged lymph nodes leads to dilatation of pulmonary lymphatics which originate in the pleura and drain towards the hilum, following interlobular septa in association with blood vessels. The stasis manifests as an early onset pleural effusion and peripheral infiltrates, representing thickened bronchovascular bundles, detectable on chest X-ray. These findings mark fully developed initial stage illness.

Acute Phase

• Ultimately, the bacteria escape from the damaged lymph nodes and invade the blood stream via the thoracic duct. Once the bacteremia and associated toxemia reach a critical level, the severe symptoms characteristic of the acute phase illness are manifested. During the acute phase illness, damage of the lung tissue becomes apparent on the X-ray. This damage results from the action of anthrax toxin on the endothelium of the lung’s capillary bed. Primary damage of the lung is not normally a feature of the initial phase illness and primary pulmonary infection is not common.

Ingestion Anthrax

Oropharyngeal anthrax

• The lesion is generally localized in the oral cavity, especially on the buccal mucosa, tongue, tonsils or posterior pharynx wall. In some cases, lesions may be present at two or more sites along the gastrointestinal tract.

• The oral lesion is generally 2-3 cm in diameter and covered with a grey pseudomembrane surrounded by extensive edema.

• When the lesion is localized on the tonsils, the affected tonsil is also intensely edematous and covered with a grey or white pseudomembrane. Tonsillar lesions may be ulcerated.

• The main clinical features are sore throat, dysphagia, and painful regional lymphadenopathy in the involved side of the neck.

• The illness may progress rapidly, and edema around the lymph node may result in extensive swelling of the neck and anterior chest wall. The overt infection leads to toxemia, acute respiratory distress and altered mental status. The patient develops acute respiratory distress syndrome and may require respiratory support. This clinical picture is followed by shock, coma and death.

• The lesion and extensive edema may lead to airway obstruction. In this situation, tracheotomy is frequently required. Even with treatment, mortality can be high.

Gastrointestinal Anthrax

• The typical eschar may occur anywhere within the gastrointestinal tract, the esophagus, stomach, duodenum, jejunum, terminal ileum or cecum, but mostly in the terminal ileum and cecum.

• The character of the lesion is generally ulcerative. There are usually multiple and superficial lesions, surrounded by edema, which may bleed. Hemorrhage may be massive and fatal, and in some cases concomitant with stomach infection. Intestinal lesions may also lead to hemorrhage, obstruction, perforation or any combination of these. Some cases are complicated with massive ascites, potentially leading to shock and death.

• Pathological examination of intestinal anthrax shows mucosal ulceration with edema, and enlarged and hemorrhagic regional lymph nodes. Necrosis is sometimes present.

• The infection may also be disseminated, and sepsis with pulmonary or meningeal involvement may result.

• The symptoms of gastrointestinal anthrax may be divided in 2 clinical forms:

• Abdominal

• Asthenia
• Headache
• Nausea
• Vomiting
• Anorexia
• Fever
• Abdominal pain
• Bloody diarrhea
• Hematemesis
• Fainting spells

• Oropharyngeal

• Fever
• Edema
• Dysphagia
• Sore throat
• Regional lymphadenopathy

• In these instances, patients will probably not seek medical treatment and, if they do, intestinal anthrax may not be considered in differential diagnosis. In some cases, approximately 24 hours later the symptoms may become severe and include acute diarrhea, nausea, vomiting, and abdominal pain.

• With progression of the illness, abdominal pain, hematemesis, bloody diarrhea, massive ascites and signs of suggestive acute abdomen (rapid increase in abdominal girth and paroxysms of abdominal pain) appear. Toxemia, sepsis and shock may develop, followed by death.

• The time between onset of symptoms to death has frequently varied from 2 to 5 days

• The incubation period is typically 1 - 6 days, although it may be as long as 10 days

• There is evidence that not all untreated cases end in toxemia, sepsis and death and that, after the initial symptoms, recovery may occur.

Complications

Cutaneous and Injection Anthrax

• Scarring
• Contracture
• Meningitis
• Coma

Gastrointestinal Anthrax

• Massive ascites
• Meningitis
• Shock
• Coma

Inhalation Anthrax

• Meningitis
• Shock
• Coma

Prognosis

• The anthrax prognosis depends on a number of factors, including:
  • The type of anthrax
  • How early the anthrax is diagnosed
  • The strain of anthrax bacteria
  • The patient's age and health condition

• Any form of anthrax is treatable, if the diagnosis is made early enough and with the appropriate supportive therapy.

• Following recovery, resolution of small- to medium-size cutaneous lesions is generally complete with minimal scarring. With larger lesions, or lesions on mobile areas, scarring and contractures may require surgical correction to return normal functioning and large cutaneous defects may require skin grafting.

Mortality

• In the non-cutaneneous forms, a correct early diagnosis is harder to reach, so these are associated with particularly high mortality. The pulmonary anthrax is the one with highest mortality rate.

• The mortality rate for each form of anthrax is:
  • Pulmonary anthrax: 45%
  • Gastrointestinal anthrax: 40%
  • Injection anthrax: 28%
  • Cutaneous anthrax: < 2%