Download Cutaneous Anthrax - UNC School of Medicine

Cutaneous Signs of
Bioterror Agents
Adam Goldstein, MD, MPH
Associate Professor
UNC Department of Family Medicine
Chapel Hill, NC
[email protected]
Objectives
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Improve ability to:
 diagnose and manage cutaneous illness
associated with suspected cases of bioterror
 Anthrax, plague, tularemia, smallpox, mustard
gas
Why worry?
“Subnational attacks using genetically
engineered organisms are inevitable”
 “Biologic agents now join nuclear agents”
 Deaths
 1 KT H-BOMB
.6M – 2M
 100 Kg ATX
1M – 3M
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(Stansfield Turner, CIA, 2001)
Anthrax
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Anthrakos = ‘coal’ b/c of black eschar
B. anthracis is gram-positive sporulating
bacillus
Spores are resistant to heat, cold, drying, &
chemical disinfection
Anthrax is endemic in western Asia (Iran
Turkey Afghanistan,) & western Africa
(McGovern, Elect Text Dermatol, 1999)
Anthrax
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Spores viable for years top 6 cm of soil & in
animal products
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Disease transmitted from infected animals or
products via skin abrasions > 90% of cases
Goats > sheep > cattle > horses > pigs > dogs
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Anthrax
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Burn dead animals, not buried, to prevent
long-term environmental contamination
History of Anthrax
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1500 B.C. -- Fifth/sixth Egyptian plagues, ? Anthrax
1600s -- "Black Bane," ? anthrax, kills 60,000 cattle
1876 -- Koch confirms bacterial origin of anthrax
1880 -- Immunization of livestock against anthrax
1915 -- German agents in U.S. inject horses/cattle with
anthrax on way to Europe during WW I
1937 -- Japan starts biological warfare program
1942 -- Britain experiments with anthrax
1943 -- U.S. begins developing anthrax weapons
1945 -- Anthrax outbreak in Iran kills 1 million sheep
Historical
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1950s and '60s -- U.S. biological program continues
1969 -- Nixon ends U.S. offensive biological program.
1970 -- Anthrax vaccine approved by U.S. FDA
1972 -- International convention outlaws development
or stockpiling of biological weapons
1978-80 -- Human anthrax epidemic strikes Zimbabwe,
infecting > 6,000 and killing 100
1979 -- Aerosolized anthrax spores released at Soviet
military facility, killing 68
1991 -- U.S. troops vaccinated for Gulf War I
1990-93 -- Terrorists release anthrax in Tokyo; no
injuries
Historical
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1995 -- Iraq produced concentrated anthrax in
biological weapons program
1998 -- U.S. approves anthrax vaccinations for all
military
2001 -- Letter with anthrax spores mailed to NBC
one week after 9/11 terrorist attacks on Pentagon &
WTC. Several die after inhaling.
Anthrax pilot plant
used to produce
billions of anthrax
spores at Fort
Detrick, Md.
U.S. ended offensive
biological weapons
research in 1969
Al Hakam,
Iraq's major
facility for
production of
biological
agents.
Plant destroyed
by Iraqi workers
in 1996.
Forms of Anthrax
Pulmonary Anthrax
Wool-sorter’s disease
 18 cases reported in U.S. 1900-1980
 Symptoms: vague prodrome with fever,
malaise, myalgias and cough
 Within days- rapidly developing precordial
discomfort, cyanosis, stridor, diaphoresis,
moist rales, pleural effusion and death
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Pulmonary Anthrax
X-ray findings: hemorrhagic mediastinitis, but
not true pneumonia; widened mediastinum
X-ray findings
Cutaneous Anthrax
Incubation period 7 days (1-12 range)
1) Initial painless papule (head, neck, extremity)
• May resemble spider bite and may itch
• Surrounding erythema & edema
2) Vesicle or bulla rapidly evolves
3) Painless hemorrhage & necrosis
• Fluid becomes black
• Lesion ulcerates & develops black eschar
with surrounding edema
• Pearl-like satellite vesicles may occur
Cutaneous Anthrax
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Lesions progress from:
 papule - erythema - vesicle - necrosis - ulcer - eschar
 with or without antibiotic therapy
 progression d/t toxin
Lesions may be solitary or multiple (same part of body)
Occasionally associated:
 Tender lymphadenopathy
 Fatigue
 Fever and/or chills
(Caruscci, JAAD 2001)
Cutaneous Anthrax - Painless Lesions
Surrounding edema or regional
lymphadenopathy may be painful.
 Debridement of skin lesions not indicated
b/c risk of spreading infection
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Cutaneous Anthrax
Cutaneous Anthrax- painless papule
Cutaneous Anthrax- vesicle with edema
Cutaneous Anthrax- early necrosis
Cutaneous Anthrax- eschar
Cutaneous Anthrax
Cutaneous Anthrax
Cutaneous Anthrax
Cutaneous Anthrax
Cutaneous Anthrax
Cutaneous Anthrax
Cutaneous Anthrax
Cutaneous Anthrax
Cutaneous Anthrax: Diagnosis
Notify local Health Department
 Before doing diagnostic tests
 Mask not required & personnel not at risk
 Disease acquired through contact with
spores, not active bacteria
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Diagnosis
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Swab exudates for Gram stain & culture (fresh vesicles)
4-mm punch biopsy full-thickness (through entire dermis)
 permanent sections
 immunohistochemistry studies
 polymerase chain reaction (PCR)
A second punch biopsy for Gram stain, bacterial, fungal &
atypical mycobacterial cultures
Send clinical history (& lesion picture if possible)
Negative bx does not r/o cut. anthrax b/c skin lesions
caused by toxins
Diagnosis
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Draw 5 mL of blood in red-topped tube
 Transfer to laboratory for isolation of serum &
subsequent storage at –70°C- label tube:
“Anthrax serology.
 Store serum at –70°C for special pick-up.”
Draw 5 mL of blood into a purple-topped tube
 Refrigerate
 Hold for pick-up- PCR diagnostic tests by CDC
Gram Stain
Culture (24-36 hours)
Differential Diagnosis: (eschar/ulceration)
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Pruritic and papular
arthropod bites
Brown recluse and other
spider bites
Pustular diseases
Antiphospholipid antibody
syndrome ulcers
Aspergillosis
Coumadin or heparin
necrosis
Ecthyma gangrenosum
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Cutaneous leishmaniasis
Mucormycosis
Plague
Rickettsial pox
Staphylococcal &
streptococcal ecthyma
Tropical ulcer
Tularemia
Typhus, scrub and tick
Differential Diagnosis: (ulceroglandular)
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Chancroid
Glanders
Herpes simplex
Cutaneous
leishmaniasis
Lymphogranuloma
venereum
Melioidosis
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Cutaneous nocardiosis
Plague
Sporotrichosis & other
deep fungal diseases
Staphylococcal &
streptococcal adenitis
Tuberculosis
Tularemia
Treatments
http://www.bt.cdc.gov/agent/anthrax/index.asp
Treatments
If suspected anthrax, begin appropriate tx
 Tx regimen differs by symptomatology
(systemic or localized), location (extremity
vs head/neck), edema (extensive or not)
 If systemic signs, head or neck location, or
extensive edema, IV therapy indicated
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Treatment for cutaneous anthrax patients without systemic
symptoms, not located on the head or neck, not with
extensive edema, & not in children younger than 2 years
Category
Adults
Initial oral therapy
Ciprofloxacin, 500 mg bid
or doxycycline, 100 mg bid
Duration (days)
60
Children
Ciprofloxacin, 15 mg/kg q12h
(not to exceed 1 g/d)
or doxycycline: >8 y o, >45 kg,
100 mg q12h; all other children,
2.2 mg/kg q12h
60
Pregnant
Ciprofloxacin, 500 mg bid (preferred) 60
or doxycycline, 100 mg bid
Immunocomp
Same
60
Treatment of cutaneous anthrax with systemic symptoms,
extensive edema, involving the head or neck, or children <
than 2 yo (same as for inhalational anthrax)
Category
IV therapy
Duration (days)
Adults
Ciprofloxacin, 400 mg q12h,
or doxycycline,100 mg q12h,
and 1-2 additional agents
IV initially, oral
when stable, 60 days
Children
Ciprofloxacin, 10 mg/kg q12h
IV initially, oral
(not to exceed 1 g/d)| or
when stable, 60 days
doxycycline: >8 y old and >45 kg,
100 mg q12h; all other, 2.2 mg/kg
q12h and 1-2 additional agents
Pregnant &
Immunocom
Same as for nonpregnant
and immunocompetent adults
& children
Same
Spider bites: Usually painful
Usually painful
 Bites from spiders of the
genus Loxoceles begin as pale
ecchymotic lesions that
rapidly turn purple.
 Lesions may ulcerate and
develop necrotic centers
 Borders are irregular, illdefined and without the
significant surrounding
edema.
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Spider bites
Plague
Boubon is Greek for groin
 Y. Pestis, 200 million deaths in history
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http://www.emedicine.com/derm/topic905.htm#target11
Plague
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Gram neg non–spore-forming coccobacillus
http://www.emedicine.com/derm/topic905.htm#target11
Plague
Tender, erythematous lymphadenopathy
 Most cases involve bubonic plague
 Tx with streptomycin, gentamicin,
tetracycline & doxycycline
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Plague
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In bloodstream causes septicemia
Tularemia
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6 clinical forms:
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ulceroglandular, glandular, oropharyngeal or gastrointestinal,
typhoidal, septicemic, and pulmonary
Sudden onset of:
 Fever, chills, headache, generalized myalgias
and arthralgias
 Incubation 2-10 days
 Ulcer generally seen at bite or inoculation site
Tularemia
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Painful, pruritic, ulcer w/ RAISED borders
Tularemia
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Ulceroglandular
80%
Tularemia
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In ‘50s and ‘60s, the U.S. made biologic
weapons containing tularemia
Streptomycin and tetracyclines are drugs
of choice
Meliodiosis
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Whitmore’s disease
Infectious disease caused by
Burkholderia pseudomallei
Endemic in SE Asia and
northern Australia
Common causative agent of
community-acquired
septicemia
(Tran, Clinical & Experimental Dermatology, 2002)
Meliodiosis
Glanders
An infectious disease caused
by bacterium Burkholderia
mallei, also called “farcy”
 Primarily affects horses
 Cutaneous via cut or scratch
in the skin, with ulceration
and pus 1-5 days at site
 No cases in U.S. > 60 years
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Mustard Gas
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Odor/taste (mustard,
garlic, onion), & color
(tan to brown to yellow)
Oily liquid is DNA
alkylating
Absorbed within minutes
Symptoms begin 2-24
hours later
Skin erythema followed
by vesicles
Mustard Gas
Mustard Gas
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Eyes develop conjunctivitis
Pulmonary symptoms- hoarseness
Death rate during World War I: 3%
Decontaminate w/ 0.5% hypochlorite (1/10 bleach to water)
Smallpox
Classic generalized exanthem
 Latin word for “spotted” referring to raised
bumps on the face and body
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http://www.bt.cdc.gov/agent/smallpox/overview/disease-facts.asp
Smallpox
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Rash, high fever & mortality rate 30%
Last natural case Somalia in 1977
Smallpox (Days 3, 5, 7)
Smallpox
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Exanthem from
vaccination
 1/100,000
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Vaccinia rash or
outbreak of sores
Generalized
vaccinia
Erythema
multiforme
http://www.bt.cdc.gov/agent/smallpox/
Smallpox
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Exanthem from
vaccination
 1/100,000
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Vaccinia rash or
outbreak of
sores
Generalized
vaccinia
Erythema
multiforme
Smallpox
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Exanthem from
vaccination
 1/100,000
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Vaccinia rash or
outbreak of sores
Generalized
vaccinia
Erythema
multiforme
Smallpox
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From
Vaccination
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1/50,000
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Eczema
vaccinatum
Progressive
vaccinia
Postvaccinal
encephalitis
Smallpox
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From
Vaccination
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1/50,000
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Eczema
vaccinatum
Progressive
vaccinia
Postvaccine
encephalitis
Monkeypox Virus
Monkeypox Virus
References
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Carucci JA, McGovern TW, Norton AS. Cutaneous anthrax
management algorithm. J Am Acad Dermatol 2001; online at:
http://www.eblue.org/scripts/om.dll/serve?action=searchDB&searchD
Bfor=art&artType=fullfree&id=a121613
Update: Investigation of bioterrorism-related anthrax and interim
guidelines for exposure management and antimicrobial therapy,
October 2001. MMWR Morb Mortal Wkly Rep 2001;50:909-19.
http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5042a1.htm
Dixon TC, Meselson M, Guillemin J, Hanna PC. Anthrax. N Engl J
Med 1999;341:815-26.
http://content.nejm.org/cgi/content/fall/341/11/815
Inglesby TV, Henderson DA, Bartlett JT, Ascher MS, Eitzen E,
Friedlander AM, et al. Anthrax as a biological weapon: medical and
public health management. Working Group on Civilian Biodefense.
JAMA 1999;281:1735-45.
http://jama.amaassn.org/issues/v281n18/ffull/jst80027.html
Thank you.