Anthrax natural history, complications and prognosis: Difference between revisions

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==Overview==
==Overview==
The natural history of anthrax depends on the mode of exposure to the disease (cutaneous, ingestion, inhalation, or injection). In cutaneous anthrax, a small painless [[skin]] sore develops into a [[blister]] and later into a [[skin ulcer]], with a central black area. The resolution of the lesion takes several weeks, depending on its size, location and severity. The anthrax lesions might lead to [[scarring]] and [[contracture]]s. Inhalation anthrax is characterized by a mild initial phase of nonspecific [[symptoms]], that is followed by sudden development of [[dyspnea]], [[cyanosis]], [[disorientation]] with [[coma]], and [[death]].<ref name=WHO>{{cite web | title = Anthrax in Humans and Animals | url = http://www.who.int/csr/resources/publications/anthrax_web.pdf }}</ref> In oropharyngeal anthrax, the lesion is generally localized in the [[oral cavity]]. This type may progress rapidly, and [[edema]] around the [[lymph node]]s may result in extensive swelling of the neck and anterior [[chest wall]].<ref name=WHO>{{cite web | title = Anthrax in Humans and Animals | url = http://www.who.int/csr/resources/publications/anthrax_web.pdf }}</ref>  The gastrointestinal anthrax lesions may occur anywhere within the [[gastrointestinal tract]], potentially bleeding, and lead to fatal [[hemorrhage]]. Some cases are complicated by massive [[ascites]],[[shock]] and death.<ref name=WHO>{{cite web | title = Anthrax in Humans and Animals | url = http://www.who.int/csr/resources/publications/anthrax_web.pdf }}</ref>  The [[prognosis]] of anthrax depends on the form of the disease, how early it is diagnosed, the [[strain]] of [[bacteria]], the patient's age and his health condition. Pulmonary anthrax has the highest [[mortality rate]].<ref name="pmid11851578">{{cite journal| author=Barakat LA, Quentzel HL, Jernigan JA, Kirschke DL, Griffith K, Spear SM et al.| title=Fatal inhalational anthrax in a 94-year-old Connecticut woman. | journal=JAMA | year= 2002 | volume= 287 | issue= 7 | pages= 863-8 | pmid=11851578 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11851578  }} </ref>


==Natural History==
==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 [[infection|infecting]] [[B. anthracis]] (usually as [[spore]]s) 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 [[vesicle]]s develops around the [[papule]]. Vesicular fluid may be exuded. Unless the patient was treated, [[Capsule (microbiology)|capsulated]] [[B. anthracis]] can be identified in appropriately stained smears of this fluid, and the [[bacterium]] can be isolated by [[cell culture|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 node]]s 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.<ref name=WHO>{{cite web | title = Anthrax in Humans and Animals | url = http://www.who.int/csr/resources/publications/anthrax_web.pdf }}</ref>


===Cutaneous Anthrax===
====Days 5-7====
Anthrax eschars are generally seen on exposed unprotected regions of the body, mostly on the face, neck, hands and wrists. Generally cutaneous lesions are single, but sometimes two or more lesions are present. For example, with infection resulting from skinning an infected dead animal, multiple lesions may be seen on hands, wrists or arms.
* 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 [[lymphadenopathy|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.<ref name=WHO>{{cite web | title = Anthrax in Humans and Animals | url = http://www.who.int/csr/resources/publications/anthrax_web.pdf }}</ref>


The incubation period ranges from as little as 9 hours to 3 weeks, mostly 2 to 6 or 7 days.  
====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]].<ref name="pmid12610093">{{cite journal| author=Spencer RC| title=Bacillus anthracis. | journal=J Clin Pathol | year= 2003 | volume= 56 | issue= 3 | pages= 182-7 | pmid=12610093 | doi= | pmc=PMC1769905 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12610093  }} </ref>


The general scenario is as follows:
====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 graft]]s, and lesions in locations such as the [[eyelid]] may require surgical intervention due to scarring.<ref name=WHO>{{cite web | title = Anthrax in Humans and Animals | url = http://www.who.int/csr/resources/publications/anthrax_web.pdf }}</ref>


* Day 0 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.
Shown below are images of the development and resolution of uncomplicated cutaneous anthrax lesion.
<gallery>
Image:Cutaneous A1.png| Day 1 of development and resolution of uncomplicated cutaneous anthrax lesion.”<SMALL><SMALL>''[http://www.who.int/en//  Adapted from World Health Organization (WHO)]''<ref name="WHO">{{Cite web | title = World Health Organization | url = http://www.who.int/en/}}</ref></SMALL></SMALL>


* Days 2-3 A small pimple or papule appears.
Image:CutaneousA2.png| Day 2 - 3 of development and resolution of uncomplicated cutaneous anthrax lesion.”<SMALL><SMALL>''[http://www.who.int/en//  Adapted from World Health Organization (WHO)]''<ref name="WHO">{{Cite web | title = World Health Organization | url = http://www.who.int/en/}}</ref></SMALL></SMALL>


* 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 oedema 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 oedema. The lesion is usually 1–3 cm in diameter and remains round and regular. Occasionally a lesion may be larger and irregularly shaped.
Image:CutaneousA3.png| Day 4 of development and resolution of uncomplicated cutaneous anthrax lesion.”<SMALL><SMALL>''[http://www.who.int/en//  Adapted from World Health Organization (WHO)]''<ref name="WHO">{{Cite web | title = World Health Organization | url = http://www.who.int/en/}}</ref></SMALL></SMALL>


* Days 5–7 the original papule ulcerates to form the characteristic eschar. topical swabs will not pick up B. anthracis. Detection in smears or by culture requires lifting the edge of the eschar with tweezers (this gives no pain unless there is secondary infection) and obtaining fluid from underneath. The fluid will probably be sterile if the patient has been treated with an antibiotic. Edema extends some distance from the lesion. Systemic symptoms are low-grade fever, malaise and headache. If the cutaneous reaction is more severe, especially if located on the face, neck or chest, clinical symptoms may be more severe with more extensive edema extending from the lesion, toxamia, a change in mental status, high fever, hypotension, regional lymphadenomegaly and the patient unable to eat or drink. Tracheotomy is a life-saving procedure in patients having a cutaneous lesion on the face or neck with an extensive oedema leading to compression on the trachea. this clini- cal manifestation is very dangerous (doganay et al., 1987; doganay, 1990).
Image:CutaneousA4.png| Day 6 of development and resolution of uncomplicated cutaneous anthrax lesion.”<SMALL><SMALL>''[http://www.who.int/en//  Adapted from World Health Organization (WHO)]''<ref name="WHO">{{Cite web | title = World Health Organization | url = http://www.who.int/en/}}</ref></SMALL></SMALL>


* 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 inef- fective. A small proportion of untreated cases develop sepsis or meningitis with hyperacute symptoms.
Image:CutaneousA5.png| Day 11 of development and resolution of uncomplicated cutaneous anthrax lesion.”<SMALL><SMALL>''[http://www.who.int/en//  Adapted from World Health Organization (WHO)]''<ref name="WHO">{{Cite web | title = World Health Organization | url = http://www.who.int/en/}}</ref></SMALL></SMALL>
Time to resolution will depend on the size, location and local severity of the lesion. The initial crust separates several weeks after 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 be expected to 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.
</gallery>


===Inhalation Anthrax===
===Inhalation Anthrax===
The term “Inhalation anthrax” has largely replaced the older names for this form of the disease, the most common of which was “pulmonary anthrax”, reflecting the fact that active infection occurs in the lymph nodes, rather than the lung itself, and that bronchopneumonia does not occur. The inhaled spores are carried by macrophages from the lungs, where there is no overt infection, to the lymphatic system where the infection progresses. Germination and initial multiplication begin within the macrophages while in transit to the lymph nodes. The vegetative cells kill the macrophages and are released into the bloodstream where they continue to multiply and lead to fatal septicemia.
====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]].  


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 typical clinical course of this form of the disease is consistent with the lesion development within the [[mediastinal]] [[lymph node]]s before the development of [[bacteraemia]]. The assault on the lung appears to be two-pronged. In the initial phase, the blockade of the [[lymphatic vessel]]s  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 vessel]]s. In the acute phase, damage associated with [[septicemia]] occurs.<ref name=WHO>{{cite web | title = Anthrax in Humans and Animals | url = http://www.who.int/csr/resources/publications/anthrax_web.pdf }}</ref>


The mild initial phase of nonspecific symptoms is followed by the sudden development of dyspnoea, cyanosis, disorientation with coma, and death.  
* [[Lymphatic]] [[stasis]] resulting from the damaged [[lymph node]]s leads to dilatation of [[pulmonary]] lymphatics which originate in the [[pleura]] and drain towards the [[hilum]], following interlobular septa in association with [[blood vessel]]s. 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.


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 oedema, 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 sep-ticaemia occurs.
====Acute Phase====
 
* Ultimately, the [[bacteria]] escape from the damaged [[lymph node]]s 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.<ref name=WHO>{{cite web | title = Anthrax in Humans and Animals | url = http://www.who.int/csr/resources/publications/anthrax_web.pdf }}</ref>
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. ultimately, the bacteria escape from the damaged lymph nodes and invade the blood stream via the thoracic duct. once the bacteraemia and associated toxaemia reach a critical level, the severe symptoms characteristic of the acute phase illness are manifest. During the acute phase illness, damage of the lung tissue becomes apparent on X-ray. this damage results from the action of anthrax toxin on the endothelium of the lung’s capillary bed (dalldorf et al., 1971). Primary damage of the lung is not normally a feature of the initial phase illness and primary pulmonary infection is an uncommon presentation.


===Ingestion Anthrax===
===Ingestion Anthrax===
====Oropharyngeal anthrax====
====Oropharyngeal anthrax====
This appears to be a relatively infrequent mani-festation in regions where ingestion anthrax is not uncommon. 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 tonsils, the affected tonsil is also intensely edematous and covered with a grey or white pseudomembrane. tonsil lesions may be ulcerated. Pharyngeal culturing is important in the diagnosis.
* The lesion is generally localized in the [[oral cavity]], especially on the buccal [[mucosa]], [[tongue]], [[tonsil]]s or posterior [[pharynx]] wall. In some cases, lesions may be present at two or more sites along the [[gastrointestinal tract]].
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 alteration in mental state. 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.
 
* 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 [[tonsil]]s, the affected [[tonsil]] is also intensely [[edema|edematous]] and covered with a grey or white pseudomembrane. [[Tonsillar]] lesions may be [[ulcer|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.<ref name=WHO>{{cite web | title = Anthrax in Humans and Animals | url = http://www.who.int/csr/resources/publications/anthrax_web.pdf }}</ref>


====Gastrointestinal Anthrax====
====Gastrointestinal Anthrax====
The gastrointestinal anthrax lesion may occur anywhere within the gastrointestinal tract - the oesophagus, stomach, duodenum, jejunum, terminal ileum or caecum, but mostly in the ileum and caecum. The character of the lesion is generally ulcerative, usually multiple and superficial, surrounded by edema. These lesions may bleed, hemorrhage may be massive and fatal, in some cases with stomach infection. Intestinal lesions may also lead to hemorrhage, obstruction, perforation or any combination of these. Some cases are complicated with massive ascites and this leads 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 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]].<ref name="pmid12610093">{{cite journal| author=Spencer RC| title=Bacillus anthracis. | journal=J Clin Pathol | year= 2003 | volume= 56 | issue= 3 | pages= 182-7 | pmid=12610093 | doi= | pmc=PMC1769905 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12610093  }} </ref>
 
*The character of the lesion is generally [[ulcer|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 [[hemorrhage|hemorrhagic]] regional [[lymph node]]s. [[Necrosis]] is sometimes present.
 
* The [[infection]] may also be disseminated, and [[sepsis]] with [[pulmonary]] or [[meningeal]] involvement may result.<ref name=WHO>{{cite web | title = Anthrax in Humans and Animals | url = http://www.who.int/csr/resources/publications/anthrax_web.pdf }}</ref>
 
* The [[symptoms]] of gastrointestinal anthrax may be divided in 2 clinical forms:<ref name="pmid12610093">{{cite journal| author=Spencer RC| title=Bacillus anthracis. | journal=J Clin Pathol | year= 2003 | volume= 56 | issue= 3 | pages= 182-7 | pmid=12610093 | doi= | pmc=PMC1769905 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12610093  }} </ref>
:* '''Abdominal'''
::* [[Asthenia]]
::* [[Headache]]
::* [[Nausea]]
::* [[Vomiting]]
::* [[Anorexia]]
::* [[Fever]]
::* [[Abdominal pain]]
::* [[Bloody diarrhea]]
::* [[Hematemesis]]
::* [[Fainting spells]]


The symptoms of gastrointestinal anthrax are initially nonspecific and include
:* '''Oropharyngeal'''
*nausea
::* [[Fever]]
*vomiting
::* [[Edema]]
*anorexia
::* [[Dysphagia]]
*fainting spells
::* [[Sore throat]]
*asthenia
::* Regional [[lymphadenopathy]]
*mild diarrhea
*fever
*headache


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, abdominal pain.  
* 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.  
* 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 from onset of symptoms to death has most frequently varied from 2 to 5 days  
* 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  
* 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 occurs.
* There is evidence that not all untreated cases end in [[toxemia]], [[sepsis]] and death and that, after the initial [[symptoms]], recovery may occur.


==Complications==
==Complications==
===Cutaneous and Injection Anthrax===
* [[Scarring]]
* [[Contracture]]
* [[Meningitis]]
* [[Coma]]
===Gastrointestinal Anthrax===
* Massive [[ascites]]
* [[Meningitis]]
* [[Shock]]
* [[Coma]]
===Inhalation Anthrax===
* [[Meningitis]]
* [[Shock]]
* [[Coma]]


==Prognosis==
==Prognosis==
The [[anthrax]] [[prognosis]] will depend on a number of factors, including:
* The [[anthrax]] [[prognosis]] depends on a number of factors, including:
*The type of [[anthrax]]
** The type of [[anthrax]]
*How early the [[anthrax]] is diagnosed
** How early the [[anthrax]] is diagnosed
*The [[strain]] of [[anthrax]] [[bacteria]]
** The [[strain]] of [[anthrax]] [[bacteria]]
*The patient's age and health condition
** 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 [[contracture]]s may require surgical correction to return normal functioning and large cutaneous defects may require [[skin graft]]ing.
 
===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.<ref name="pmid11851578">{{cite journal| author=Barakat LA, Quentzel HL, Jernigan JA, Kirschke DL, Griffith K, Spear SM et al.| title=Fatal inhalational anthrax in a 94-year-old Connecticut woman. | journal=JAMA | year= 2002 | volume= 287 | issue= 7 | pages= 863-8 | pmid=11851578 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11851578  }} </ref>
 
* The mortality rate for each form of anthrax is:
** Pulmonary anthrax: 45%<ref name="pmid11851578">{{cite journal| author=Barakat LA, Quentzel HL, Jernigan JA, Kirschke DL, Griffith K, Spear SM et al.| title=Fatal inhalational anthrax in a 94-year-old Connecticut woman. | journal=JAMA | year= 2002 | volume= 287 | issue= 7 | pages= 863-8 | pmid=11851578 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11851578  }} </ref>
** Gastrointestinal anthrax: 40%<ref name="pmid14609791">{{cite journal| author=Beatty ME, Ashford DA, Griffin PM, Tauxe RV, Sobel J| title=Gastrointestinal anthrax: review of the literature. | journal=Arch Intern Med | year= 2003 | volume= 163 | issue= 20 | pages= 2527-31 | pmid=14609791 | doi=10.1001/archinte.163.20.2527 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14609791  }} </ref>
** Injection anthrax: 28%<ref name=NHS>{{cite web | title = An Outbreak of Anthrax Among Drug Users in Scotland, December 2009 to December 2010 | url = http://www.documents.hps.scot.nhs.uk/giz/anthrax-outbreak/anthrax-outbreak-report-2011-12.pdf }}</ref>
** Cutaneous anthrax: < 2%<ref name=CDC>{{cite web | title = Centers for Disease Control and Prevention Expert Panel Meetings on Prevention and Treatment of Anthrax in Adults | url = http://wwwnc.cdc.gov/eid/article/20/2/13-0687_intro }}</ref>


==References==
==References==
{{reflist|2}}
{{reflist|2}}


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Latest revision as of 16:38, 18 September 2017

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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 exposure to the disease (cutaneous, ingestion, inhalation, or injection). In cutaneous anthrax, a small painless skin sore develops into a blister and later into a skin ulcer, with a central black area. The resolution of the lesion takes several weeks, depending on its size, location and severity. 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 sudden development of dyspnea, cyanosis, disorientation with coma, and death.[1] In oropharyngeal anthrax, the lesion is generally localized in the oral cavity. This type may progress rapidly, and edema around the lymph nodes may result in extensive swelling of the neck and anterior chest wall.[1] The gastrointestinal anthrax lesions may occur anywhere within the gastrointestinal tract, potentially bleeding, and lead to fatal hemorrhage. Some cases are complicated by massive ascites,shock and death.[1] The prognosis of anthrax depends on the form of the disease, how early it is diagnosed, the strain of bacteria, the patient's age and his health condition. Pulmonary anthrax has the highest mortality rate.[2]

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

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.[1]

Days 5-7

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.[3]

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.[1]

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

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.

Acute Phase

Ingestion Anthrax

Oropharyngeal anthrax

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

Gastrointestinal Anthrax

  • The symptoms of gastrointestinal anthrax may be divided in 2 clinical forms:[3]
  • Abdominal
  • Oropharyngeal
  • The time between onset of symptoms to death has frequently varied from 2 to 5 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

Gastrointestinal Anthrax

Inhalation Anthrax

Prognosis

  • 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.[2]
  • The mortality rate for each form of anthrax is:
    • Pulmonary anthrax: 45%[2]
    • Gastrointestinal anthrax: 40%[4]
    • Injection anthrax: 28%[5]
    • Cutaneous anthrax: < 2%[6]

References

  1. ↑ 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 1.11 1.12 1.13 1.14 "Anthrax in Humans and Animals" (PDF).
  2. ↑ 2.0 2.1 2.2 Barakat LA, Quentzel HL, Jernigan JA, Kirschke DL, Griffith K, Spear SM; et al. (2002). "Fatal inhalational anthrax in a 94-year-old Connecticut woman". JAMA. 287 (7): 863–8. PMID 11851578.
  3. ↑ 3.0 3.1 3.2 Spencer RC (2003). "Bacillus anthracis". J Clin Pathol. 56 (3): 182–7. PMC 1769905. PMID 12610093.
  4. ↑ Beatty ME, Ashford DA, Griffin PM, Tauxe RV, Sobel J (2003). "Gastrointestinal anthrax: review of the literature". Arch Intern Med. 163 (20): 2527–31. doi:10.1001/archinte.163.20.2527. PMID 14609791.
  5. ↑ "An Outbreak of Anthrax Among Drug Users in Scotland, December 2009 to December 2010" (PDF).
  6. ↑ "Centers for Disease Control and Prevention Expert Panel Meetings on Prevention and Treatment of Anthrax in Adults".
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